Proctitis

Proctitis is is defined as a condition of  inflammation of the anus and the lining of the rectum (i.e., the distal 10–12 cm) of that can lead to bowl discomfort, bleeding, a discharge of mucus or pus, etc.

I. Causes and Risk factors
A. Types of Cause of Proctitis
Types of Proctitis are depending to the underlined causes of the diseases
1. Radiation proctitis
The condition is the result of exposure to x-rays or other ionizing radiation
 
2. Ischemic proctitis
According to the study by the University of Illinois at Chicago/Metropolitan Group Hospitals-St. Francis Hospital, Ischemic injury to the rectum is rare owing to its rich vascular supply, and is seldom seen in clinical practice(1). There is a report of Six patients with acute ischemic proctitis; four cases occurred after direct arterial interruption, one after accidental embolization of the blood supply to the rectum, and one from tumor edema. Bloody diarrhea was the most common symptom. Loss of anal sphincter tone was also an early sign in three patients(2).  
 
3. Ulcerative proctitis
Epidemiological studies have shown that ulcerative proctitis represents 25-55% of ulcerative colitis. In western countries, the incidence of ulcerative proctitis has been increased, while the incidence of more extensive colitis remained unchanged. Ulcerative proctitis has shown to be a benign disease, with a prevalence of local symptoms, less systemic and extraintestinal manifestations, and low endoscopic grades of activity(3).

4. Sexually transmitted proctitis
Gastrointestinal manifestations of sexually transmitted infections (STI) are common. Proctitis, or inflammation of the rectum, has several infectious and non‐infectious causes, the infectious pathogens typically being sexually acquired. Chlamydia, gonorrhoea, herpes simplex virus and syphilis are among the STI that can cause anorectal disease, and more recently outbreaks of less common infections such as lymphogranuloma venereum (LGV)(4).

5. Autoimmune disease
Systemic lupus erythematosus (SLE) is an autoimmune disease, due to the body's immune system mistakenly attacks healthy tissue. Ischaemic colitis is relatively uncommon in systemic lupus erythematosus (SLE). There is a report of a a 38-year-old woman, who presented with haematochezia which subsequently proved to be due to ischaemic proctitis with a large rectal ulcer in a case that was subsequently diagnosed as SLE, according to the study by the Nil Ratan Sircar Medical College(4a).

6. Non-sexually transmitted infection
The classical example of non-sexually transmitted infection occurs in children and is caused by the same bacteria that cause strep throat(4b).

B. Rick factors
1. Low abdominal pain, high inflammatory lesions and an family history
According to the study by Hôpital Pontchaillou, of the Endoscopic information obtained for 52 patients with ulcerative proctitis (23 F, 29 H) seen during a ten-year period. The median follow-up was 68 +/- 8 months, showed that low abdominal pain, an family history of ulcerative colitis, and high inflammatory lesions at referral were significantly associated with a higher risk of extension(5).

2. Young age of onset of symptoms, smoking and appendectomy
According to the study of "Course and natural history of idiopathic ulcerative proctitis in adults" by Università degli Studi di Brescia Cattedra di Chirurgia Generale, Young age of onset of symptoms, smoking and appendectomy are associated with an increased risk of extension of the disease(6).

3.  Sexual behavior(7)
a. Men having sex with men (MSM)
Sexually transmitted infection (STI) screening programmes are implemented in many countries to decrease burden of STI and to improve sexual health. In a study of a total of 1455 consultations in MSM showed that the prevalence of C. trachomatis and N. gonorrhoeae per anatomic site was: urethral infection 4.0% respectively and 2.8%, oropharynx 1.5% and 4.2%, and anorectum 8.2% and 6.0%. The majority of chlamydia cases (72%) involved a single anatomic site, which was especially manifest for anorectal infections (79%), while 42% of gonorrhoea cases were single site. Twenty-six percent of MSM with anorectal chlamydia and 17% with anorectal gonorrhoea reported symptoms of proctitis; none of the oropharyngeal infections were symptomatic. Most cases of anorectal infection (83%) and oropharyngeal infection (100%) would have remained undiagnosed with a symptom-based protocol.

b. Others
If you have multiple partners, , don't use condoms and have sex with a partner who has an STI, you are as an increased risk to develop proctitis.

4. Inflammatory bowel diseases
Risk of proctitis is increased with patient with IBD. In the study of a total of 1,255 filled questionnaires received with 96 were rejected and 1,159 (92.3 %),  this comprised data on 745 (64.3 %) patients with UC, 409 (35.3 %) with CD, and 5 with indeterminate colitis. The median duration of illness was longer in patients with CD (48 months) compared to those with UC (24 months) (p = 0.002), found that more than one half of patients (UC 51.6 %, CD 56.9 %) had one or more extraintestinal symptoms. A definite family history of IBD was present in 2.9 % (UC 2.3 % and CD 4.6 %; p = 0.12). The extent of disease in UC was pancolitis 42.8 %, left-sided colitis 38.8 %, and proctitis alone in 18.3 %(8).

5. Cancer radiation therapy
According to the study by the University of Minnesota Hospital and Clinics, a high posterior rectal dose (> 5,000 cGy) is associated with increased prevalence of proctitis after radiation therapy(9).

6. Socioeconomic factors, dietary and other personal habits, and medical history 
In the study of the risk factors for extensive ulcerative colitis and ulcerative proctitis of a total of 167 (98%) of all prevalent cases of ulcerative colitis diagnosed in Uppsala county from 1945 to 1964 and 167 age and sex matched population, showed that ulcerative colitis patients were less likely than controls to be current cigarette, pipe, or cigar smokers (odds ratio (OR) = 0.44; 95% confidence limits (CL) = 0.25-0.78), but more likely to have symptoms induced by drinking milk (OR = 4.63; 95% CL = 2.15-9.93). Patients with ulcerative colitis do not differ in most of the socioeconomic, dietary and personal habits compared with the background population(10).

7. Frequent fecal impactions
Frequent fecal impactions without proper treatment are associated toincreased risk of proctitis, according to the study by the Ohio University(10a).

 II. Symptoms
1. Rectal bleeding and anal discomfort
There is a report of a A 45-year-old man was referred to our surgical clinic for investigation of rectal bleeding and anal discomfort. is a sexually transmitted infection caused by Chlamydia trachomatis. There are few reports describing rectal stricture as a late complication of chronic proctitis associated with lymphogranuloma venereum (LGV) infection. Lymphogranuloma venereum (LGV)proctitis is often mild, but chronic cases can be associated with serious complications. If LGV is misdiagnosed or partially treated, the natural history of chronic long-lasting inflammation of the rectum may include the development of fissures, perianal abscess and strictures of the rectum(11).

2. Change of Singapore General Hospital
According to the Singapore General Hospital study of review, 77 patients were admitted for the treatment of radiation proctitis, with a median follow-up period of 14 (range 1-61) months. There were 23 male and 54 female patients, with a median age of 63.9 (range 37-89) years, the most common presenting symptom was bleeding per rectum (89.6 percent), with a change in bowel habits a distant second (10.4 percent)(12).

2. Constipation
There is a report of a 72-year-old white woman presenting with a large abdominal mass, who had at least 4 episodes of radiographically demonstrated fecal impaction over the previous year without adequate treatment. The patient required hospitalization for a bleeding rectal ulcer during the second episode of fecal impaction. Computed tomography (CT) scans on this admission revealed a dilated colon up to 16 x 14 cm in maximal dimensions extending over 30 cm, filled with massive fecal material, according to the study by the College of Osteopathic Medicine, Ohio University, Athens(13).

3. Urgency, diarrhea, and tenesmus
According to the study of 50 patients to compare colonic irrigation and oral antibiotics (irrigation group) versus 4% formalin application (formalin group) for treatment of hemorrhagic radiation proctitis by Chulalongkorn University, Bangkok, showed that treatment with daily self-administered colonic irrigation with 1 L of tap water and a 1-week period of oral antibiotics (ciprofloxacin and metronidazole) indicated a a significant improvement in rectal bleeding and bowel frequency in both treatment groups, but significant improvement in urgency, diarrhea, and tenesmus was demonstrated only in the irrigation group(15).

4. Anorectal pain, discharge and change in stool frequency
The University Hospital, Zurich, Switzerland report a study since 2003, there are twelve cases of proctitis, all in men having sex with men (MSM), caused by the LGV serovar L2 C. In the observation of trachomatis, of the overall 11 patients the majority were HIV positive and only 2 were HIV negative. Only one patient reported previous sexual contacts outside Europe (Thailand) as the likely place of infection. The clinical presentation was characterised by anorectal pain, discharge, tenesmus and change in stool frequency(16).

5. Blood in stool
In most cases, blood in stool is presented for patient with ulcerative proctitis.

6. Ulcers, and occasionally lymphadenopathy and fever
Symptoms of infectious proctitis can include rectal blood and mucous discharge, anorectal pain, ulcers, and occasionally lymphadenopathy and fever, according to the study by the University of Chicago Medical Center(14)

IV. Complications and diseases associated with Proctitis
A. Complications
A.1. Diseases complications
1. Intractable bleeding, intestinal obstruction or intra-abdominal sepsis
In the  review of 77 patients admitted for the treatment of radiation proctitis, with a median follow-up period of 14 (range 1-61) months. There were 23 male and 54 female patients, with a median age of 63.9 (range 37-89) years.the majority of the patients (72.5 percent) received non-surgical treatment, most commonly using topical 4 percent formalin solution to arrest the bleeding, with more than half the patients requiring repeat treatments. 14 (18.2 percent) patients required colorectal resections for intractable bleeding, intestinal obstruction or intra-abdominal sepsis(17).

2. Syphilis
There is a first report of a case of with simultaneous manifestations of proctitis, gastritis, and hepatitis. The diagnosis of syphilitic proctitis and gastritis was established by the demonstration of spirochetes with anti-Treponema pallidum antibody staining in biopsy specimens. Unusual manifestations of secondary syphilis completely resolved after 4 weeks of antibiotic therapy(18).

3. Bleeding areas in the rectum, internal and/or external hemorrhoids
According to the study by, Surgeons are appropriately concerned about using conventional methods of treatment in patients with radiation proctitis, such as cautery for complications of bleeding areas in the rectum, rubber band ligation, or excision of internal and/or external hemorrhoids, for fear of poor healing and possible exacerbation of the original problem(19).

4. Comstipation
According to the study by University La Sapienza,  constipation in ulcerative proctitis (UP), may be correlated with rectal fibrosis, which reduces the transit of stools from the left colon. The concomitance of asymptomatic anorectal organic or functional alteration may contribute to worsen constipation(20).

5. Increased irritation to the anal and rectal area in patients with proctitis.

6. Etc.

A.2. Complications after treatment
1. Formalin installation treatment
Inn the study to evaluate the results of formalin installation treatment in terms of outcome and complications with a solution of 4% formalin was introduced in aliquots of 50 ml kept in contact with the mucosa for 30 s and then cleared away using saline irrigation; five to six aliquots were used in each session, showed that in a mean follow-up of 18 months (range 6-26), two patients had repeat episodes of bleeding, one underwent successful repeat irrigation, and the other refused further treatment. One patient suffered from severe anococcygeal pain and worsening of incontinence after the procedure. The pain was treated with lidocaine ointment and sitz baths with partial success. Another patient developed severe formalin-induced colitis 5 days after the procedure, which required intravenous antibiotics and hydration. Formalin installation may be effective in controlling refractory bleeding due to radiation induced proctitis(21).

2. Systemic isotretinoin therapy
Isotretinoin's best-known and most dangerous side effect is birth defects due to in utero exposure. There is a report of complications of anal fissure, rectal bleeding and proctitis with the systemic isotretinoin therapy(22).

3. Etc.

B. Diseases associated with Proctitis
1. Inflammatory bowel diseases (IBD) and sexual transmitted infections
Proctitis is a common problem and is most frequently associated with inflammatory bowel diseases (IBD). However, in the last ten years the incidence of infectious proctitis appears to be rising, especially in men who have sex with men. This may be due to the rise of people participating in receptive anal sex as well as the increase in sexually transmitted infections, such as those from Chlamydia trachomatis, Neisseria gonorrhoeae, Herpes simplex virus and Treponema pallidum. Recent outbreaks of lymphogranuloma venereum among homosexual men throughout Europe highlight the need to consider sexually transmitted infections in the differential diagnosis of proctitis, according to the study by the University of Florence(23).

2. Procitis associated with chlamydial infection
According to the University of Sydney, New South Wales. an aged koala presented for euthanasia was found to have asymptomatic chronic proctitis, cystitis, prostatitis, urethritis and conjunctivitis associated with chlamydial infection. Inflammation was severe in the terminal rectum and extended into the proximal common vestibule. Chlamydial organisms were visualised in the rectal surface epithelium using Giminez' stain and an immunoperoxidase staining method. Organisms were also detected in the epithelium of the bladder, prostate and urethra(24). Other in the study to investigate the prevalence and genotype distribution of Chlamydia trachomatis infection among men who have sex with men (MSM), 145 MSM from two sauna settings in Shenzhen, China were invited to participate in this study during September 2008 and May 2009, showed that the prevalence of anorectal chlamydial infection was 24% in the study population and was significantly associated with proctitis symptoms(25).

3. Human immunodeficiency virus infection
There is a report of a of published cases and a recently managed patient is presented, which describes the clinical features of cytomegalovirus proctitis. About half of the reports describe sexually transmitted cytomegalovirus proctitis following anal intercourse, which typically presents with rectal bleeding and a mononucleosis-like syndrome. This condition resolves spontaneously and may be associated with human immunodeficiency virus infection(26).

4. Immune-mediated diseases
In the study to to evaluate the prevalence of pANCA expression and its association with clinical findings and disease course in Korean patients with UC, included 484 patients with UC who were diagnosed and treated between 1990 and 2006 at Severance Hospital, Yonsei University, Seoul, Korea, showed that the prevalence of pANCA expression in Korean patients with UC was relatively low compared to that in Western countries. Although UC patients with pANCA expression had more severe clinical findings at diagnosis and higher cumulative relapse rates in our study, further prospective studies are warranted to clarify whether pANCA positivity influences the initial clinical presentation or disease aggressiveness(27).

5. Hermansky Pudlak syndrome
Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder consisting of oculocutaneous albinism, platelet dysfunction and systemic complications associated with lipofuscin deposition in the reticuloendothelial system. According to Auxilio Mutuo Hospital, Rio Piedras, there is a report of a series of two patients with HPS treated in Puerto Rico, and the results from medical and surgical intervention for gastrointestinal disease. Our experience with HPS patients has shown the difficult management of perineal disease similar in the management of Crohn's. However, complications from the bleeding diathesis necessitate caution during surgery and potential anesthesia complications(28).

6. Crohn's disease
There is a report of four patients with Crohn's disease who underwent fecal diversion with an in situ rectum were observed in whom sigmoidoscopy was initially normal at the time of the diversion, became distinctly abnormal during the year after the diversion, and then returned to normal within 3 mo following reestablishment of intestinal continuity. The entity of nonspecific diversion proctitis might account for this phenomenon independently or by accelerating the Crohn's disease process, according to the study(29).

7. Etc.

V. Misdiagnosis and Diagnosis
A. Misdiagnosis
1. Hirschsprung's disease
Allergic proctitis and abdominal distention mimicking Hirschsprung's disease in infants.In the study to determine the incidence and clinical aspects of allergic proctitis (AP) in infants with symptoms that mimic Hirschsprung's disease (HD), found that in the infants with severe abdominal distention, the incidence of AP mimicking HD was relatively high. Therefore, consideration of AP should be part of the differential diagnosis in infants with severe abdominal distention or findings that mimic HD. For differentiation of these disorders, a rectal suction biopsy is very useful.In the infants with severe abdominal distention, the incidence of AP mimicking HD was relatively high. Therefore, consideration of AP should be part of the differential diagnosis in infants with severe abdominal distention or findings that mimic HD. For differentiation of these disorders, a rectal suction biopsy is very useful(30).

2. Diffuse cavernous haemangioma of the rectum (DCHR)g masquerading 
Diffuse cavernous haemangioma of the rectum (DCHR) is a rare benign vascular neoplasm that affects mainly young adults and can present with rectal bleeding or massive haemorrhage.  There is a report of a case of DCHR masquerading as proctitis which was diagnosed many years ago following colonoscopy, according to St. George's Hospital NHS Trust, London(31).

3. Colitis cystica profunda and solitary rectal ulcer syndrome-polyoid variant 
Colitis cystica profunda and solitary rectal ulcer syndrome-polyoid variant are related chronic benign disorders with characteristic histological features. There is a report of a case of colitis cystica profunda and solitary rectal ulcer syndrome-polypoid variant that was misdiagnosed initially as an ulcerative proctitis, according to the study by Ben-Gurion University of the Negev, Beer-Sheva, Israel(32).

4. Rectal strictures
Rectal strictures are uncommon in young patients without a history of malignancy, inflammatory bowel disease or previous surgery. It presents with nonspecific symptoms, rectal ulcer, proctitis, anal fissures, abscesses and rectal strictures. Clinical and endoscopic findings as well as histology resemble Crohn's disease, which may be misdiagnosed/ According to the study by King's College Hospital, rectal lymphogranuloma venereum is a rare cause of rectal strictures but surgeons should be aware of its existence and include it in the differential diagnosis of unexplained strictures in high-risk patients(33).

5. Etc.

B. Diagnosis
1. Stool sample
The aim of the stool examination is to find out types of bacterial causes of infection.
Unfornunately, Non-invasive diagnostic tools to evaluate the severity of acute, radiation-induced proctitis are not readily available, but faecal calprotectin and lactoferrin concentrations could be markers of acute, radiation-induced proctitis(34).

2. Blood test
The aim of the blood test is also to determine the types of infection as well as blood loss

3. Proctoscopy
Proctoscopy procedure in which yuor doctor insert a thin tube containing a camera and a light to visually inspect to look for sign of proctitis. In a prospective study of 130 patients who underwent external radiation therapy (RT) for stage T1 to T4 prostate cancer between 1997 and 2008, to determine the Role of Early Proctoscopy in Predicting Late Symptomatic Proctitis After External Radiation Therapy for Prostate Carcinoma, Proctoscopy showed that In patients with acute endoscopic proctitis (AEP) and Acute clinical proctitis (ACP), the risk of late clinical proctitis (LCP)  was more than 5-fold increased compared to those who were asymptomatic, while a much smaller increase in risk occurred in patients with ACP only. Early proctoscopy can provide valuable information regarding the likelihood of late(35).

4. Rectal culture
Rectal culture is the laboratory test  of normally involves a swab of patients rectum with an aim to determine types of bacterial causes of proctitis.

5. Rectal microscopy
The Microstructure imaging of human rectal mucosa may be helpful in determination the causes of the disease. According to the study by the Urinary Medicine, Mortimer Market Centre, in all, 134/136 had rectal microscopy of whom, 47/134 (35%) were smear-positive for Rectal gonorrhoea (GC) . Of the 136 cases, 90 received antibiotics for GC at their first presentation. Twenty-four of 90 (27%) would not have been treated until culture results were available, if rectal microscopy had not been performed. The results suggest that rectal microscopy remains an important tool and increases the proportion of men treated for GC at their first attendance(36).

6. Sigmoidoscopy
Sigmoidoscopy is a procedure of using a flexible tube called a sigmoidoscope with a small camera attached to the end placed through the anus and gently moved into your colon for examination of up to the sigmoid.  Dr. McMillan A. in the study to to assess the value of sigmoidoscopy in the routine investigation of homosexual men, this procedure was undertaken on 1118 men who attended a sexually transmitted diseases clinic as "new" or "return new" patients, indicated that Serious rectal disease was not identified in any of the 557 men who were symptomless at the initial attendance. Though the extent of the proctitis diagnosed in 166 men would not have been defined, 99% (465) of 470 anorectal lesions would have been identified if proctoscopy alone had been performed. It is concluded that sigmoidoscopy does not have a role in the routine investigation of homosexual men(37).

VI. Preventions
A. Diet to prevent Proctitis
1. Black and green tea
Gallocatechin, containing catechin is phytochemicals of Flavan-3-ols, in the group of Flavonoids (polyphenols), found abundantly in green  and black tea. In the evaluation of the anti-inflammatory and antimicrobial effect of nanocatechin on CBP and plasma concentration of catechins in an animal model, found that the use of ciprofloxacin, catechin, and nanocatechin showed statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the control group. The nanocatechin group showed statistically significant decrease in bacterial growth and improvement in prostatic inflammation compared with the catechin group. Plasma concentrations of epicatechin, gallocatechin gallate, and epigallocatechin gallate were significantly higher in the nanocatechin group than those in the catechin group. These results suggest that nanocatechin has better antimicrobial and anti-inflammatory effects on rat CBP than catechin due to higher absorption into the body, according to "Anti-inflammatory and antimicrobial effects of nanocatechin in a chronic bacterial prostatitis rat model" by Yoon BI, Ha US, Sohn DW, Lee SJ, Kim HW, Han CH, Lee CB, Cho YH(38).
Other In the identification of tea polyphenols were evaluated for their ability to inhibit enterovirus 71 (EV71) replication in Vero cell culture, found that The viral inhibitory effect correlated well with the antioxidant capacity of polyphenol. Mechanistically, EV71 infection led to increased oxidative stress, as shown by increased dichlorofluorescein and MitoSOX Red fluorescence. Upon EGCG treatment, reactive oxygen species (ROS) generation was significantly reduced. Consistent with this, EV71 replication was enhanced in glucose-6-phosphate dehydrogenase deficient cells, and such enhancement was largely reversed by EGCG, according to "Antiviral effect of epigallocatechin gallate on enterovirus 71" by Ho HY, Cheng ML, Weng SF, Leu YL, Chiu DT(39).

2. Apple skin
Quercetin is a member of flavonoids, found abundantly in apple skin It is also one of antioxidants with property of protecting our body in fighting against forming of free radicals cause of mutation of cells`DNA. According to the study of `Antimicrobial and cytotoxic activities of leaves, twigs and stem bark of Scutia buxifolia Reissek.`by Boligon AA, Janovik V, Frohlich JK, Spader TB, Forbrig Froeder AL, Alves SH, Athayde ML. (Source from a Phytochemical Research Laboratory, Department of Industrial Pharmacy , Federal University of Santa Maria , Build 26, room 1115 , Santa Maria , CEP 97105-900 , Brazil.), posted in PubMed, researchers found that quercitrin, isoquercitrin and rutin were identified by HPLC and may be partially responsible for the antimicrobial activities observed. This study reports for the first time the antimicrobial and cytotoxic activities of S. buxifolia leaves, twigs and stem bark.
Also according to the study of `Antioxidant and Anti-Inflammatory Activities of Quercetin 7-O-β-D-Glucopyranoside from the Leaves of Brasenia schreberi.`by Legault J, Perron T, Mshvildadze V, Girard-Lalancette K, Perron S, Laprise C, Sirois P, Pichette A. (Source from Laboratory for Analysis and Separation of Plant Species (LASEVE), Université du Québec à Chicoutimi , Chicoutimi, Québec, Canada.), posted in PubMed, researchers found that some flavonoids have been reported to possess beneficial effects in cardiovascular and chronic inflammatory diseases associated with overproduction of nitric oxide. Quercetin-7-O-β-D-glucopyranoside possesses anti-inflammatory activity, inhibiting expression of inducible nitric oxide synthase and release of nitric oxide by lipopolysaccharide-stimulated RAW 264.7 macrophages in a dose-dependent manner. Quercetin-7-O-β-D-glucopyranoside also inhibited overexpression of cyclooxygenase-2 and granulocyte macrophage-colony-stimulating factor.

3. Tomatoes
Tomato is a red, edible fruit, genus Solanum, belongs to family Solanaceae, native to South America. Because of its health benefits, tomato is grown world wide for commercial purpose
and often in green house. Tomato is considered as antiseptic natural foods including natural antiseptic agent ascorbic acid that helps to enhance the immune system in guarding our body against the possibility of infection, sepsis, or putrefaction, according to the article of "The 7 Benefits Of Drinking Lemon Water" posted in Simple Health Cures. Other study indicated that Lycopene, one of the powerful antioxidant in tomatoes, not only helps the immune system in neutralizing the forming of free radicals in the body and according to Harvard investigation as it found that men who ate more than 10 servings tomato-based foods daily (like cooked tomatoes and tomato sauce,) had a 35 percent lower risk of developing prostate cancer than those who ate the least amount of these foods. The benefits of lycopene was more pronounced with advanced stages of prostate cancer. Also according to the study of "Chemoprevention of prostate cancer with lycopene in the TRAMP model" by Konijeti R, Henning S, Moro A, Sheikh A, Elashoff D, Shapiro A, Ku M, Said JW, Heber D, Cohen P, Aronson WJ., posted in PubMed(40)

4. Fennel
Fennel is a species of Foeniculum Vulgare, belong to the family Apiaceae (Umbelliferae), and native to to the shores of the Mediterranean. It is now widely cultivated all around the globe to use as food and herb. In the determination of the chemical compositions of the essential oil and hexane extract isolated from the inflorescence, leaf stems, and aerial parts of Florence fennel found that the essential oil, anethole, and hexane extract were effective against most of the foodborne pathogenic, saprophytic, probiotic, and mycotoxigenic microorganisms tested. The results of the present study revealed that (E)-anethole, the main component of Florence fennel essential oil, is responsible for the antimicrobial activity , according to "Antimicrobial activities of essential oil and hexane extract of Florence fennel [Foeniculum vulgare var. azoricum (Mill.) Thell.] against foodborne microorganisms" by Cetin B, Ozer H, Cakir A, Polat T, Dursun A, Mete E, Oztürk E, Ekinci M(41).
Other In the study of fennel honey, ethanol, and aqueous propolis extracts orally and theirs effect on immune defense found that all tested previously bee product-immunized rats could significantly challenge the induced S. aureus infection (P < .01). The effects were more pronounced in rats that had received fennel honey solution, according to "Immune defense of rats immunized with fennel honey, propolis, and bee venom against induced staphylococcal infection" by Sayed SM, Abou El-Ella GA, Wahba NM, El Nisr NA, Raddad K, Abd El Rahman MF, Abd El Hafeez MM, Abd El Fattah Aamer A(42).

B. Phytochemicals and antioxidants to prevent Proctitis
1. Theaflavin-3-gallate
Theaflavin-3-gallate, a theaflavin derivative, is phytochemicals of Flavan-3-ols, in the group of Flavonoids (polyphenols) found abundantly in black tea. In the comparison of TF derivatives (theaflavin (TF(1)), theaflavin-3-gallate (TF(2)A), theaflavin-3'-gallate (TF(2)B), and theaflavin-3,3'-digallate (TF(3))) in scavenging reactive oxygen species (ROS) in vitro, indicated that positive antioxidant capacities of TF(2)B on singlet oxygen, hydrogen peroxide, hydroxyl radical, and the hydroxyl radical-induced DNA damage in vitro were found, according to "Evaluation of the antioxidant effects of four main theaflavin derivatives through chemiluminescence and DNA damage analyses" by Wu YY, Li W, Xu Y, Jin EH, Tu Y(43).
 Other In the evaluation of the antimicrobial activities of seven green tea catechins and four black tea theaflavins, found that (-)-gallocatechin-3-gallate, (-)-epigallocatechin-3-gallate, (-)-catechin-3-gallate, (-)-epicatechin-3-gallate, theaflavin-3, 3'-digallate, theaflavin-3'-gallate, and theaflavin-3-gallate showed antimicrobial activities at nanomolar levels; (ii) most compounds were more active than were medicinal antibiotics, such as tetracycline or vancomycin, at comparable concentrations; (iii) the bactericidal activities of the teas could be accounted for by the levels of catechins and theaflavins as determined by high-pressure liquid chromatography; (iv) freshly prepared tea infusions were more active than day-old teas; and (v) tea catechins without gallate side chains, gallic acid and the alkaloids caffeine and theobromine also present in teas, and herbal (chamomile and peppermint) teas that contain no flavonoids are all inactive, according to "Antimicrobial activities of tea catechins and theaflavins and tea extracts against Bacillus cereus" by Friedman M, Henika PR, Levin CE, Mandrell RE, Kozukue N(44). 

2. Allyl sulfides
Garlic has been used in traditional Chinese and herbal medicine over thousands of year as antibacterial, antiviral, and antifungal agent and in treating other conditions such as parasites, respiratory problems, poor digestion, low energy, etc. In many studies, researchers found that Allyl sulfides, a phytochemical in garlic has been demonstrated effectively in treating certain diseases.
According to the article of "GARLICTHE BOUNTIFUL BULB" by Carmia Borek, Ph.D. posted in Life extension magazine, the author indicated that human studies confirm immune stimulation by garlic. Subjects receiving aged garlic extract at 1800 mg a day for three weeks showed a 155.5% increase in natural killer immune cell activity that kills invaders and cancer cells. Other subjects receiving large amounts of fresh garlic of 35g a day, equivalent to 10 cloves, showed an increase of 139.9%. In six weeks, patients with AIDS receiving aged garlic extract showed an enhancement of natural killer cells from a seriously low level to a normal level.

3. Piperine
Piperine is a phytochemical alkaloid in the class of organosulfur compound, found abundantly in white and black pepper, long pepper, etc. In the valuation of novel synthetic analogues of piperine as inhibitors of multidrug efflux pump NorA of Staphylococcus aureus, showed that a newly identified class of compounds derived from a natural amide, piperine, is more potent than the parent molecule in potentiating the activity of ciprofloxacin through the inhibition of the NorA efflux pump. These molecules may prove useful in augmenting the antibacterial activities of fluoroquinolones in a clinical setting, according to "Novel structural analogues of piperine as inhibitors of the NorA efflux pump of Staphylococcus aureus" by Ashwani Kumar, Inshad Ali Khan, Surrinder Koul, Jawahir Lal Koul, Subhash Chandra Taneja, Intzar Ali, Furqan Ali, Sandeep Sharma, Zahid Mehmood Mirza, Manoj Kumar, Pyare Lal Sangwan, Pankaj Gupta, Niranjan Thota and Ghulam Nabi Qazi(45) 
Other In the investigation of investigate the anti-inflammatory effect of piperine against adjuvant-induced arthritis in rats, an experimental model for rheumatoid arthritis and compared it with that of the non-steroidal anti-inflammatory drug indomethacin, found that Histopathological analysis of joints also revealed that synovial hyperplasia and mononuclear infiltration observed in arthritic rats were alleviated by piperine. Thus, the present study clearly indicated that piperine possesses promising anti-inflammatory effect against adjuvant-induced arthritis by suppressing inflammation and cartilage destruction, according to "Anti-inflammatory Effect of Piperine in Adjuvant-Induced Arthritic Rats-a Biochemical Approach" by Murunikkara V, Pragasam SJ, Kodandaraman G, Sabina EP, Rasool M(46). 

4. Sinigrin
Sinigrin is a phytochemical glucosinolate, belongs to the family of glucosides found abundantly in Brussels sprouts, broccoli, the seeds of black mustard, etc. In the investigation of Allyl isothiocyanate (AIT) derived from the glucosinolate sinigrin found in plants of the family Brassicaceae and its antimicrobial agent against a variety of organisms, including foodborne pathogens such as Escherichia coli O157:H7, found that it can be postulated that: 1) AIT is a more effective antimicrobial at low pH values and its degradation reduces this activity; 2) decomposition products in water might not participate in the antimicrobial action of AIT; and 3) AIT seems to have a multi-targeted mechanism of action, perhaps inhibiting several metabolic pathways and damaging cellular structures, according to "Enzymatic inhibition by allyl isothiocyanate and factors affecting its antimicrobial action against Escherichia coli O157:H7" by Luciano FB, Holley RA(47).
Other  In the examination of the effect of an aqueous extract of cooked Brussels sprouts on formation of 7-hydro-8-oxo-2'-deoxyguanosine (8-oxodG) in calf thymus DNA in vitro, found that Sinigrin, a glucosinolate abundant in Brussels sprouts, co-eluted with the most effective fraction and had DNA protective effects. In comparison with other antioxidants the patterns of effect of the extract in the five damage systems were more similar to that of sodium azide than to those of dimethylsulfoxide and vitamin C, according to "Inhibition of oxidative DNA damage in vitro by extracts of brussels sprouts" by Zhu C, Poulsen HE, Loft S(48).

VI. Treatments
A. In conventional medicine perspective
Medical treatment of proctitis depends on the etiology
A.1. Radiation proctitis
A.1.1. Acute radiation proctitis 
Acute radiation proctitis usually does not require treatment as the diseases can resolve after several months. Topical mesalazine is contraindicated during radiotherapy. Hydrocortisone enema is not superior to sucralfate in preventing acute rectal toxicity.. According to the study to assess whether the topical use of steroids or 5-aminosalicylic acid (5-ASA) is superior to sucralfate in preventing acute rectal toxicity during three-dimensional conformal radiotherapy (3DCRT) to 76 Gy(63),
A.1.2. Chronic radiation proctitis
Chronic radiation proctitis is the result of damage to the blood vessels which supply the colon due to radiotherapy. 
1. Non surgical interventions
Chronic radiation proctitis (inflammation of the rectum) may develop after the completion of pelvic radiotherapy. In Studies (preferentially randomised controlled trials) of interventions for the non-surgical management of late radiation proctitis in patients who have undergone pelvic radiotherapy as part of their cancer treatment, indicated that Late radiation complications are a relatively rare manifestation, with many potential carers and poor diagnostic criteria. Although certain interventions look promising and may be effective (such as rectal sucralfate, adding metronidazole to the anti-inflammatory regime and heater probes), single small studies (even if well conducted) provide insufficient evidence(64).

2. Surgical interventions
 a. Cryospray Ablation
Radiation proctitis, a common condition associated with radiotherapy for the treatment of pelvic cancers, is characterized by difficult to manage rectal pain and bleeding. According to the study by the Uniformed Services University of the Health Sciences, Cryotherapy is an effective method in the management of chronic radiation proctitis with minimal complications(65).

b. Radio frequency ablation (RFA)
Radiation proctitis is a frequent complication of pelvic radiation for cancer.  There is a report of a case of refractory radiation proctitis, with suboptimal response to other therapies, treated successfully with a novel method, radiofrequency ablation(66).

A.2.  Ischemic proctitis
A.2.1. Acute ischemic proctitis
1. Non surgical interventions, include
a. Superficial mucosal ischemia
Superficial mucosal ischemia was treated without surgery, but deeper levels of necrosis required laparotomy and Hartmann's resection. Rectal excision was not necessary. Four patients survived the ischemic event(67).

b. Formalin instillation
Topical (4 percent) formalin is safe and effective in treatment of radiation-induced hemorrhagic proctitis. A single treatment will stop bleeding in 75 percent of patients(68). Other study also indicated that there is a case of an elderly male with multiple medical problems and hemorrhagic, ischemic proctitis is presented. The proctitis was refractory to all other medical options but responded to topical instillation of 4 percent formalin(69).

 2. Surgical interventions include
 a. Proctectomy
There is a report of four cases of acute ischemic proctitis that required complete proctectomy. All patients had large vessel atherosclerosis with rectal bleeding and sepsis as the presenting signs and symptoms. Three of four patients underwent complete proctectomy as the initial procedure. The fourth patient underwent complete proctectomy five days after the initial intervention. Two of four patients survived and were ultimately discharged from the hospital. A third patient recovered from surgery but ultimately died of respiratory complications. Only the patient who was initially treated by subtotal proctectomy died as the result of the disease. Although ischemic necrosis of the rectum is rare, complete proctectomy may be necessary to save the patient's life(70).

b. Transcatheter embolization
In the study of treatment of lower gastrointestinal bleeding was attempted in 13 patients by selective embolization of branches of the mesenteric arteries with Gelfoam, showed that One patient improved after embolization but bleeding recurred within 24 hours and in another patient the catheterization was unsuccessful. Five patients with diverticular hemorrhage were embolized in the right colic artery four times, and once in the middle colic artery. Three patients had embolization of the ileocolic artery because of hemorrhage from cecal angiodysplasia, post appendectomy, and leukemia infiltration. Three patients had the superior hemorrhoidal artery embolized because of bleeding from unspecific proctitis, infiltration of the rectum from a carcinoma of the bladder, and transendoscopic polypectomy(71).


A.2.2. Chronic ischemic proctitis
1. Non surgical treatments
In the study to identify the various non-surgical treatment options for the management of late chronic radiation proctitis and evaluate the evidence for their efficacy, showed that Sixty-three studies met the inclusion criteria, including six randomised controlled trials that described the effects of anti-inflammatory agents in combination, rectal steroids alone, rectal sucralfate, short chain fatty acid enemas and different types of thermal therapy(72).

2. Surgical interventions include
1. Laparoscopic colorectal surgery
In the study to assess the outcome of laparoscopic colorectal surgery in patients >60 years of age and compare it to a younger group of patients who underwent similar procedures, indicated that here were no statistically significant differences between the younger and older groups relative to the incidence of complications (11 vs 14%, respectively) and conversion (8 vs 11%, respectively) or the length of ileus (2.8 vs 4.2 days, respectively) or hospitalization (5.2 vs 6.5 days, respectively) (P = NS for all). There was no mortality in either group. The outcome of laparoscopic colorectal surgery in older patients is similar to that noted in younger patients. Advanced age should not be a contraindication to laparoscopic colorectal surgery(73).

2. Laparoscopic or laparoscopic-assisted colorectal operations
There were 140 laparoscopic and laparoscopic-assisted procedures performed between May 1991 and January 1995. The mean patient age was 48 (range 12-88) years; there were 78 males and 62 females. Indications for surgery included inflammatory bowel disease in 47, colorectal carcinoma in 19, diverticular disease in 17, polyps in 16, familial polyposis in 7, colonic inertia in 7, fecal incontinence in 11, sigmoidocele in 3, irradiation proctitis in 3, rectal prolapse in 2, intestinal lymphoma in 2, and miscellaneous conditions in 6. The procedures included 38 total abdominal colectomies (TAC) (ileoanal reservoir 28, ileorectal anastomosis 8 and end ileostomy 2); 70 segmental resections of the colon, small bowel, and rectum(74)

A.1.3. Ulcerative proctitis  
1. Non surgical treatments  
Ulcerative proctitis is an important and increasingly common subcategory of ulcerative colitis (UC) in which inflammation is limited to the rectum. According to the study by the McGill University Health Centre, treatment options include the oral and/or rectal 5-aminosalicylate (5-ASA) preparations. Rectal therapy delivering higher concentrations of active medication (5-ASA or glucocorticoids) directly to the inflamed mucosa while minimizing systemic absorption provides a highly effective and safe treatment. Oral glucocorticoids are indicated in patients who are resistant to or intolerant of 5-ASA therapy. Immunomodulators have an important role in individuals with glucocorticoid dependent or glucocorticoid refractory disease(75).

2. Surgical treatments
In case of severity, surgery may be necessary. According to the study by the, Severe UC is defined as more than 6 bloody stools per day and signs of systemic involvement (fever, tachycardia, anemia). These patients should be hospitalized for intensive treatment and surveillance (ECCO EL 5, RG D) as the development of a toxic megacolon and perforation is a potentially life-threatening condition. Intravenous steroids (e.g. methylprednisolone 60 mg/d or hydrocortisone 400 mg/d) remain the mainstay of conventional therapy to induce remission (ECCO EL 1b, RG D; DGVS C). Patients refractory to maximal oral treatment with prednisolone and 5-ASA can be given the tumor necrosis factor (TNF)-α blocker IFX at 5 mg/kg (ACG EL A). Nevertheless, colectomy rates are as high as 29% in patients with severe UC and who need intravenous corticosteroids. They should therefore be presented to the colorectal surgeon on the day of admission. It is crucial that gastroenterologists and surgeons provide joint daily care in order to avoid delaying the necessary surgical therapy(76).

A.1.4. Sexually transmitted proctitis
1. Non surgical interventions(77)
Treatment can be started empirically while awaiting the microbiological results, thus reducing inflammation, infection duration and hence infectivity of the patient. The appropriate treatment of sexually transmitted proctitis has important implications in the control of HIV by reducing both HIV transmission and susceptibility.
a. Azithromycin (1 g as a single dose) or doxycycline (100 mg twice daily for a week) is an effective treatment for chlamydia. 
b. HIV‐positive men with proctitis should be treated for LGV in the first instance. The preferred treatment is doxycycline 100 mg twice daily for 3 weeks; erythromycin may be used as an alternative.
c. Homosexual men with symptomatic rectal chlamydia should be given LGV treatment until the serovar is determined.
d. The treatment of gonorrhoea depends on local guidelines, based on surveillance of resistance patterns of the organism. A minimum criterion is that at least 95% of gonorrhoea prevalent in a population should be susceptible to the antibiotic used
e. Patients with recurrent symptoms of HSV may benefit from long‐term suppressive treatment. Early syphilis is treated with intramuscular procaine penicillin (10 days) or benzathine penicillin (2.4 g as a single dose). Doxycycline can be used in patients allergic to penicillin (100 mg twice daily for 2 weeks). Longer courses of antibiotics are used for latent syphilis.

2. Surgical interventions include Appendicectomy
In the report of  a prospective case series of 30 adult patients (median age 35 years, range 17-70 years; male/female: 11/19) with ulcerative proctitis (median duration of symptoms 5 years, range 8 months to 30 years; median Simple Clinical Colitis Activity Index score 9, range 7-12), who underwent appendicectomy in the absence of any history suggestive of previous appendicitis, showed that the report so far provides rationale for controlled trials to properly evaluate the possible role of appendicectomy in the treatment of ulcerative proctitis(78). 

A.1.5. Autoimmune disease
Non surgical and surgical interventions
The development of ischemic colitis in patients with SLE is an uncommon complication. But widespread fibrinoid vasculitis, typical of SLE, is thought to be a likely predisposing factor. If this vasculitis involves the colon, ischemic colitis occurs. Gastrointestinal vasculitis is one of the most serious complications of SLE, even though the occurrence of colonic lesions is rare (0.2%). The gastrointestinal vasculitis of SLE is consequence of tissue damage from vasculopathy mediated by immune complexes, and has been associated with SLE activity. There are no pathognomic and histopathologic findings in SLE; however, pathologic changes associated with gastrointestinal vasculitis occur in the small vessels of the intestinal wall rather than in medium-sized mesenteric arteries. Ischemic colitis in patients with SLE is caused by decreased blood perfusion of mesenteric vasculatures. The predisposing factors are embolism, thrombosis, vasospasm, drugs (steroids and immunosuppressive agents), vasculitis, performed colonoscopy, and enema. Management of abdominal manifestations of SLE, in the absence of compelling radiographic or clinical findings suggestive of infarction or perforation, are steroid, antibiotics, and fluid therapy, According to the study by the The Catholic University of Korea(79).


 
B. In Herbal medicine perspective
The aim of herbal treatment is strenghten the immune sytem of the body to fight off the invasion of bacterial causes of the diseases
1. Echinacea, Ashwagandha and Brahmi
Herbs, as food or medicine, can strengthen the body and increase its resistance to illnesses by acting on various components of the immune system. In the study to compare the efficacy of Echinacea, Ashwagandha and Brahmi in strenghten the immune system, showed that Herbal remedies based on Echinacea, Brahmi, or Ashwagandha can enhance immune function by increasing immunoglobulin production. Furthermore, these herbal medicines might regulate antibody production by augmenting both Th1 and Th2 cytokine production(49).

2. Cinnamon
In administration of popular herb used in traditional medicine to treat various disorders such as chronic gastric symptoms, arthritis, and the common cold and its immunomodulatory effect found that observations provided evidence that CWE was able to down-regulate IFN-γ expression in activated T cells without altering IL-2 production, involving inhibition of p38, JNK, ERK1/2, and STAT4, according to the study of "Immunomodulatory effect of water extract of cinnamon on anti-CD3-induced cytokine responses and p38, JNK, ERK1/2, and STAT4 activation" by Lee BJ, Kim YJ, Cho DH, Sohn NW, Kang H. (50)
. Other in the observation of three natural essential oils (i.e., clove bud oil, cinnamon oil, and star anise oil) and their antimicrobal effects found that the cinnamon oil-chitosan film had also better antimicrobial activity than the clove bud oil-chitosan film. The results also showed that the compatibility of cinnamon oil with chitosan in film formation was better than that of the clove bud oil with chitosan, according to the study of "Synergistic Antimicrobial Activities of Natural Essential Oils with Chitosan Films" by Wang L, Liu F, Jiang Y, Chai Z, Li P, Cheng Y, Jing H, Leng X.(51) 
3. Green Tea
In the assessment of unregulated activity of these receptors could lead to autoimmune diseases and the effects of green tea catechin, epigallocatechin gallate of the study of "Green tea catechin, epigallocatechin gallate, suppresses signaling by the dsRNA innate immune receptor RIG-I." by Ranjith-Kumar CT, Lai Y, Sarisky RT, Cheng Kao C., researchers found that EGCG and its derivatives could have potential therapeutic use as a modulator of RIG-I mediated immune responses by binding RIG-I and inhibits its signaling at low micromolar concentrations in HEK293T cells(52)
Other In the observation of green tea and rosemary leaf powders on the growth of microorganisms of the study of "Inhibitory effect of commercial green tea and rosemary leaf powders on the growth of foodborne pathogens in laboratory media and oriental-style rice cakes' by Lee SY, Gwon SY, Kim SJ, Moon BK.[13c], researchers indicated that 1 or 3% green tea or rosemary to rice cakes did not significantly reduce total aerobic counts; however, levels of B. cereus and S. aureus were significantly reduced in rice cakes stored for 3 days at room temperature (22 degrees C) and that suggested the use of natural plant materials such as green tea and rosemary could improve the microbial quality of foods in addition to their functional properties(53).

4. Turmeric
Turmeric is a perennial plant in the genus Curcuma, belonging to the family Zingiberaceae, native to tropical South Asia. The herb has been used in trditional medicine as anti-oxidant, hypoglycemic, colorant, antiseptic, wound healing agent, and to treat flatulence, bloating, and appetite loss, ulcers, eczema, inflammations, etc.
In the explore more systematically in various diseases of curcumin's therapeutic promise,
indicated that curcumin may be particularly suited to be developed to treat gastrointestinal diseases. This review summarizes some of the current literature of curcumin's anti-inflammatory, anti-oxidant and anti-cancer potential in inflammatory bowel diseases, hepatic fibrosis and gastrointestinal cancers, according to "Therapeutic potential of curcumin in gastrointestinal diseases" by Rajasekaran SA(54).
Other In the research of a literature search (PubMed) of almost 1500 papers dealing with curcumin, most from recent years, with ll available abstracts were read and pproximately 300 full papers were reviewed, found that curcumin, a component of turmeric, has been shown to be non-toxic, to have antioxidant activity, and to inhibit such mediators of inflammation as NFkappaB, cyclooxygenase-2 (COX-2), lipooxygenase (LOX), and inducible nitric oxide synthase (iNOS). Significant preventive and/or curative effects have been observed in experimental animal models of a number of diseases, including arteriosclerosis, cancer, diabetes, respiratory, hepatic, pancreatic, intestinal and gastric diseases, neurodegenerative and eye diseases, "Curcumin, an atoxic antioxidant and natural NFkappaB, cyclooxygenase-2, lipooxygenase, and inducible nitric oxide synthase inhibitor: a shield against acute and chronic diseases" by Bengmark S(55).

C. In traditional Chinese medicine perspective
1. Xilei-san
Xilei-san is a traditional Chinese herbal medicine that has proven to be of possible use in the treatment of ulcerative proctitis. In the study to compare the efficacy of  Xilei-san with dexamethasone enemas in subjects with mild-to-moderate active UP, showed that  Xilei-san enemas are comparable to dexamethasone enemas in this study. This medicine is safe, well accepted, and may be an alternative drug in the treatment of mild-to-moderate active UP(56).

2. The Erkang capsule
Shi-Quan-Da-Bu-Tang is a traditional Chinese herbal medicine formula used to increase vital energy, and strengthen health and immunity.  The Erkang capsule is a modified formula of Shi-Quan-Da-Bu-Tang, with the addition of four other herbs to increase the adaptogen effects and ergogenic properties. In mice study, the Erkang treated group had significant differences in mortality, body weight change, fatigue, cold temperature endurance, and immune function related organ weight change, compared to the control animals(57).

3. Lingzhi
Reishi mushroom or Lingzhi is a fungal species in the genus Ganoderma, belonging to the family Ganodermataceae, native to Asia. The herb has been use in traditional medicine as anti-caners and anti inflammatory, antioxdant agent and to enhance immune function, treat hepatitis B virus, protect against neuron degeneration, etc. In the demonstration of Ganoderma lucidum, a medicinal fungus is thought to possess and enhance a variety of human immune functions, found that Our current results of analyzing rLZ-8-mediated signal transduction in T cells might provide a potential application for rLZ-8 as a pharmacological immune-modulating agent, according to "Reishi immuno-modulation protein induces interleukin-2 expression via protein kinase-dependent signaling pathways within human T cells" by Hsu HY, Hua KF, Wu WC, Hsu J, Weng ST, Lin TL, Liu CY, Hseu RS, Huang CT(58).  Other In the investigation of the water-soluble, polysaccharide components of Reishi (designated as MAK) in murine colitis induced by trinitrobenzene sulphonic acid (TNBS), found that MAK-stimulated PMs produced GM-CSF in a dose-dependent manner. Intestinal inflammation by TNBS was improved by feeding with MAK. MLNs of mice treated with TNBS produced IFN-γ, which was inhibited by feeding with MAK. In contrast, MLNs of mice treated with TNBS inhibited GM-CSF production, which was induced by feeding with MAK and conculded that that the induction of GM-CSF by MAK may provide the anti-inflammatory effect, according to "The water-soluble extract from cultured medium of Ganoderma lucidum (Reishi) mycelia (Designated as MAK) ameliorates murine colitis induced by trinitrobenzene sulphonic acid" by Hanaoka R, Ueno Y, Tanaka S, Nagai K, Onitake T, Yoshioka K, Chayama K(59).

4. Ren Shen
Ren Shen is also known as Gingshen. The smells aromatic, tastes sweet and slightly warm herbs had been used in TCM as improved immune system, Anti Cancer, Anti aging, Anti stress, etc. agent and to generates fluids and reduce thirst, for xinqixu (heart qi deficient) palpitations with instant sweating and anxiety, insomnia, dizziness/headache, forgetfulness, impotence, diabetes, bleeding in the vagina not during period, seizures in children, chronic weakness, etc. as it strongly tonifies Original Qi, tonifies the Spleen and the Lungs, promotes generation of Body Fluids, calms thirs and the Mind, etc. by enhancing the functions of spleen and lung. In the study of Water-soluble ginseng oligosaccharides (designated as WGOS) with a degree of polymerization ranging from 2 to 10 were obtained from warm-water extract of Panax ginseng roots, found that WGOS were potent B and T-cell stimulators and WGOS-1 has the highest immunostimulating effect on lymphocyte proliferation among those purified fractions. It is hoped that the WGOS will be developed into functional food or medicine, according to "Structural characterization and immunological activities of the water-soluble oligosaccharides isolated from the Panax ginseng roots" by Wan D, Jiao L, Yang H, Liu S(60). Other In the evaluation of the extraction conditions of polysaccharides from the rhizomes of Panax japonicus C.A. Meyer and its antioxidant effect found that antioxidant activity exhibited Panax japonicus polysaccharides (PJP) had a good potential for antioxidant, according to "Optimization of polysaccharides from Panax japonicus C.A. Meyer by RSM and its anti-oxidant activity" by Wang R, Chen P, Jia F, Tang J, Ma F(61).

5. Qingre Buyi Decoction
In the study to investigate the efficiency, safety, and possible mechanisms of Qingre Buyi Decoction (QBD) in the treatment of acute radiation proctitis (ARP), showed that Addition of QBD to the conventional treatment can effectively alleviate the damage of intestinal mucosal barrier function and improve all main clinical symptoms and signs of the ARP. The combination of conventional treatment with Chinese herbal medicine QBD is effective and safe for ARP.(62).

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