evaluation of an ulcerative coloproctitis-colorectal cancer (uc-crc) model and efficacy of liujunzi decoction (ljzd)

Liujunzi 달인: UC-CRC 예방을 위한 효과적인 치료

Colorectal cancer (CRC) is a common gastrointestinal malignancy, the third most common malignancy, and the second most common cause of death in the world, accounting for 10% of the global cancer incidence and 9.4% of the total cancer-related death1,2. Genetic factors, chronic inflammation, high-fat diet, diabetes, and abnormal intestinal flora are risk factors for CRC3,4. Among them, inflammatory bowel disease, especially ulcerative coloproctitis (UC), is a clear risk factor for CRC5,6. UC-associated CRC (UC-CRC) is a transition process of inflammation, atypical hyperplasia, and cancer based on chronic inflammation of the colorectum, which is different from the typical adenoma-adenocarcinoma development model of CRC7,8. Compared with the general population, the risk of CRC is approximately 10-40 times higher in patients with inflammatory bowel disease9.
Currently, surgery is still the standard treatment for CRC, and depending on the location and stage of the tumor, radiation therapy, systemic drug therapy, or a combination of both are possible10. Although these traditional treatment modalities have made great progress, due to the high heterogeneity and recurrence rate of CRC, the prognosis is poor, and the treatment effect is not ideal11,12. Therefore, early detection, early diagnosis, and comprehensive treatment are key to improving the survival rate of CRC patients, and it is particularly important to pay attention to the transformation of UC to CRC. Over the years, traditional Chinese medicine (TCM) has attracted much attention in the treatment of UC-CRC or chronic gastritis due to its limited side effects and significant efficacy. Based on dialectical treatment, famous Chinese medicine practitioners of various generations have created a large number of classic prescriptions, such as Huangqi Jianzhong decoction13, Sijunzi decoction14, and Sishen pill15.
Liujunzi decoction (LJZD) originated from the works of Yi Xue Zheng Zhuan compiled in the Ming Dynasty and is a classic prescription in TCM16. As shown in Table 1, LJZD consists of six traditional herbs, including Codonopsis pilosula (Franch.) Nannf. (Dangshen), Poria cocos (Schw.) Wolf (Fuling), Atractylodes macrocephala Koidz. (Baizhu), Glycyrrhiza uralensis Fisch. (Gancao), Citrus reticulata Blanco (Chenpi) and Pinellia ternata (Thunb.) Breit (Banxia), which has the effect of replenishing qi and strengthening the spleen, drying dampness, and resolving phlegm. In modern clinical practice, it is often used to treat chronic gastritis, gastric ulcers, and duodenal ulcers. Modern pharmacological research has shown that LJZD and modified LJZD have high application value in the adjuvant treatment of UC and digestive tract cancer17,18,19.
At present, there are many ways to construct UC-CRC mouse models, but the azoxymethane (AOM)/dextran sulfate sodium (DSS) induced mouse model is the most widely used UC-CRC model; the clinical symptoms, morphological, and pathological observations have proved that the model is very similar to human UC-CRC20,21. The basic principle is to first induce carcinogenesis with chemical carcinogen AOM and then continuously expose mice to the inflammatory stimulation environment of DSS to simulate the continuous damage and repair of intestinal mucosal epithelium, thereby constructing a UC-CRC mouse model22. The aim of this study is to establish a mouse model of UC-CRC by intraperitoneal injection of AOM and cyclic stimulation of DSS in the short term and to evaluate the effect of the drug and the molecular mechanism of LJZD on UC-CRC in order to provide a scientific basis for the treatment of UC-CRC.

저자 스포트라이트: 대장막염 암에 대한 중국 전통 치료법으로서의 Liujunzi 달인

생쥐의 대장염 암 모델 확립 및 한의학 치료 효과 평가

This study was on the prevention and treatment of coloproctitis cancer with traditional Chinese medicine. We aim to establish a mouse model for coloproctitis cancer and evaluate traditional Chinese medicine indicators. We confirmed that the Chinese medicine Liujunzi decoction is a effective treatment for coloproctitis cancer prevention.In the future, we will work to identify more sensitive biomarkers for colon and rectal cancer and screen Liujunzi decoction for therapeutic targets.

Watch this Scientific Journal Video about Evaluation of an Ulcerative Coloproctitis-Colorectal Cancer UC-CRC Model and Efficacy of Liujunzi Decoction LJZD at JoVE.com

궤양성 대장염-대장암(UC-CRC) 모델 평가 및 Liujunzi 달임(LJZD)의 효능

시작하려면 UC-CRC 마우스 모델을 설정하고 준비된 LJZD 및 5-ASA 솔루션을 각 그룹에 관리합니다. 약물 치료 후 적응 섭식 시작부터 약물 치료가 끝날 때까지 매일 쥐의 체중을 모니터링합니다. 각 실험용 쥐의 대변 농도를 부지런히 관찰하고 문서화하여 정상, 묽은 변 또는 묽은 설사로 분류합니다.실험 동물에서 관찰된 모든 분변 출혈을 주의 깊게 문서화하여 출혈 없음, 최소 출혈 또는 대변에 피가 보이는 것으로 분류합니다. 결장 직장 조직을 분리하려면 안락사된 마우스를 극저온 해부학적 환경 내에서 유지합니다. 쥐를 누운 자세로 고정합니다.가위를 사용하여 하복부 털을 다듬고 해당 부위를 에탄올로 소독합니다. 눈꺼풀 집게를 사용하여 두 허벅지 뿌리와 복부 정중선 사이의 교차점을 부드럽게 잡습니다. 그런 다음 가위를 사용하여 1-1.5cm 길이의 가로 절개를 만듭니다.횡방향 절개의 중간 지점에서 시작하여 xiphoid 돌기까지 복부의 정중선을 따라 세로 절개를 수행합니다. 대장 주위 조직을 항문 쪽으로 조심스럽게 분리하여 대장 항문과 주변 조직을 분리합니다. 복부 피부를 부드럽게 옆으로 밀어 대장이 완전히 노출되도록 합니다.눈꺼풀 집게를 사용하여 복강에서 결장직장을 추출하고 항문에서 맹장으로 절개합니다. 채취한 대장 조직을 섭씨 4도의 식염수에 보관합니다. UC-CRC 모델군은 대조군에 비해 상당한 체중 감소를 보였으며, 이는 LJZD 치료로 완화되었습니다.LJZD 치료는 UC-CRC 모델군에 비해 질병 활성도 지수를 개선했다.

evaluation-an-ulcerative-coloproctitis-colorectal-cancer-uc-crc-model

Research

JoVE Journal

Medicine

Evaluation of an Ulcerative Coloproctitis-Colorectal Cancer (UC-CRC) Model and Efficacy of Liujunzi Decoction (LJZD)

44 조회수.  Changchun University of Chinese Medicine. 시작하려면 UC-CRC 마우스 모델을 설정하고 준비된 LJZD 및 5-ASA 솔루션을 각 그룹에 관리합니다. 약물 치료 후 적응 섭식 시작부터 약물 치료가 끝날 때까지 매일 쥐의 체중을 모니터링합니다. 각 실험용 쥐의 대변 농도를 부지런히 관찰하고 문서화하여 정상, 묽은 변 또는 묽은 설사로 분류합니다.실험 동물에서 관찰된 모든 분변 출혈을 주의 깊게 문서화하여 출혈 없음, ?...

비디오: 궤양성 대장염-대장암(UC-CRC) 모델 평가 및 Liujunzi 달임(LJZD)의 효능

Establishment of Coloproctitis Cancer Model in Mice and Evaluation of Therapeutic Effect of Chinese Medicine

Colorectal cancer (CRC) is a common malignancy of the digestive system and has become the third most common malignancy worldwide and the second leading cause of malignancy-related death. Ulcerative coloproctitis (UC) is a precancerous lesion, and UC-associated CRC (UC-CRC) is the most common subtype of CRC. Therefore, a reasonable UC-CRC model is the cornerstone and guarantee of new drug development. Traditional Chinese medicine (TCM) has been widely used in the treatment of UC-CRC due to its good efficacy. As a classic tonic prescription of TCM, Liujunzi decoction (LJZD) has been widely used in the treatment of UC-CRC. In this study, a UC-CRC model was established by combining azomethane and dextran sulfate sodium, and the LJZD was administered. The data confirmed that LJZD can effectively inhibit cancer transition in UC-CRC by using mouse body weight, colorectal length, pathological and inflammatory factors, colorectal barrier function, and cancer markers. This protocol provides a system for evaluating the efficacy of TCM in the prevention and treatment of UC-CRC.

This protocol provides a mouse model of ulcerative coloproctitis-associated colorectal cancer induced by azomethane combined with dextran sulfate sodium. The model was used to evaluate the efficacy of traditional Chinese medicine compounds in the prevention and treatment of colorectal cancer.

Colorectal cancer (CRC) is a common malignancy of the digestive system and has become the third most common malignancy worldwide and the second leading ...

연구

의학

Preparation of Liujunzi Decoction (LJZD) for the Treatment of Ulcerative Coloproctitis-Colorectal Cancer  (UC-CRC)

To begin place Dang Shen, Bai Zhu, into a specialized ceramic pot. Add 1000 milliliters of distilled water and let it soak at room temperature for one hour. Using a grinder, grind 12 grams of Fu ling into a fine powder.Then, soak the powdered Fu ling in 300 milliliters of distilled water in a separate container for one hour at room temperature. Mix the prepared Chinese herbal mixture in the specialized ceramic pot. Boil the mixture and maintain it over medium heat until the decoction volume reduces to 300 milliliters.Combine the filtrate obtained from the decoction and continue boiling until the volume reduces to 150 milliliters. Then centrifuge the concentrated liquid at 10, 000 G for five minutes. Concentrate the obtained supernatant to 30 milliliters over medium heat.Transfer the final concentrate to a dish and dry it using an electric drying oven until only the solute remains as a powder. Now, weigh the obtained powder, and dissolve it in sterile distilled water to create the daily dosage for mice. To prepare five amino salicylic acid, weigh 64 milligrams of five amino salicylic acid powder, and dissolve it in 200 milliliters of sterile distilled water.

궤양성 대장암-대장암(UC-CRC) 치료를 위한 류쥔지 달임(LJZD) 제제

Establishment of an Ulcerative Coloproctitis-Colorectal Cancer (UC-CRC) Model to Evaluate the Therapeutic Effect of Chinese Medicine

To begin, gently position the mouse with its belly up and the head slightly down. Grasp the back skin to secure the abdominal area and insert a one milliliter syringe needle, one centimeter to the right of the midline of the abdomen at the intersection of the line, connecting both thighs. Gradually insert the one milliliter syringe needle to a depth of three to five millimeters under the skin.Insert the needle approximately 0.3 to 0.5 millimeters into the abdominal cavity at a 45 degree angle. Once the needle tip passes through the abdominal muscle, notice a sudden decrease in resistance. Slowly inject 0.1 milliliters of the azoxymethane injection solution per 10 grams of body weight into the mice.Subsequently, retract the syringe gently. Then add 500 milliliters of sterile distilled water to 10 grams of DSS. To prepare a 2%DSS solution.Mix the solution with a vortex mixer and store at four degrees Celsius until use, administer the prepared LJZD and five amino salicylic acid solution daily at a consistent time via gastric gavage to the respective groups at week seven and week 15.

한의학의 치료 효과를 평가하기 위한 궤양성 대장염-대장암(UC-CRC) 모델 구축

To begin, establish the UC-CRC mouse model and administer the prepared LJZD and 5-ASA solution to the respective groups. After the drug treatment, monitor the weight of mice daily from the beginning of adaptive feeding until the end of drug treatment. Diligently observe and document the fecal consistency of each experimental mouse, categorizing it as normal, loose stools or watery diarrhea.Carefully document any fecal bleeding observed in the experimental animals, categorizing it into no bleeding, minimal bleeding, or visible blood in the stool. To separate the colorectal tissue, maintain the euthanized mice within a cryogenic anatomical environment. Secure the mice in a supine position.Using scissors, trim the lower abdominal hair and sterilize the area with ethanol. Using eyelid forceps, gently grasp the intersection point between the two thigh roots and the abdominal midline. Then use scissors to create a one to 1.5 centimeters long transverse incision.Perform a longitudinal incision along the median line of the abdomen, starting from the midpoint of the transverse incision to the xiphoid process. Carefully detach the peri-colorectal tissues in the direction towards the anus, separating the colorectum rom the surrounding tissue. Gently push aside the abdominal skin to fully expose the colorectum.Using eyelid forceps, extract the colorectum from the abdominal cavity and section it from the anus to the cecum. Preserve the collected colorectal tissues in saline at four degrees Celsius. The UC-CRC model group had a significant weight loss compared to the control group which was alleviated by LJZD treatment.LJZD treatment improved the disease activity index compared with the UC-CRC model group.