Ancient Chinese Medicine Herbal Formula Huanglian Jiedu Decoction as a Neoadjuvant Treatment of Chemotherapy by Improving Diarrhea and Tumor Response

Abstract

Background: Diarrhea is a major gastrointestinal complication in cancer patients receiving chemotherapy. Prognosis and treatment of chemotherapy-induced diarrhea (CID) remain unsatisfactory. This study aims to explore the potential of an ancient Chinese Medicine herbal formula Huanglian Jiedu Decoction (HLJDD) as an adjuvant treatment on CID. Method: HLJDD extract was prepared by GMP manufacturing standard with quality and stability being checked. 5-fluorouracil (5-Fu) and irinotecan (CPT-11)-induced diarrhea model in mice was established and pre-, co-and post-treatment of HLJDD was implemented. Mechanism of action was explored by detecting related protein expression. In addition, the effect of HLJDD on diarrhea and tumor response induced by clinical regimens FOLFOX and FOLFIRI was measured in murine orthotopic colorectal cancer model. Results: HLJDD exhibited consistency in quality and stability after 24-month storage. Pre-treatment of HLJDD, but not co-treatment or post-treatment, could significantly improve the diarrhea score, body weight loss and intestinal damage in 5-Fu-and CPT-11-treated mice. Pre-treatment of HLJDD reduced cell apoptosis in the intestine of chemotherapy-treated mice, and promoted renewal of intestinal cell wall. CD44 was predicted as the potential target of HLJDD-containing compounds in CID. HLJDD pretreatment induced presentation of CD44-postive cells in the intestine of chemotherapytreated mice, and initiated expression of stemness-associated genes. Transcriptional products of the downstream Wnt signaling of CD44 were elevated. Furthermore, pre-treatment of HLJDD could significantly improve the tumor response of clinical chemotherapy regimens FOLFOX and FOLFIRI in orthotopic colorectal cancer, and reduce diarrhea and intestinal damage. Conclusion: Our study suggests the potential of HLJDD as a neoadjuvant treatment of chemotherapy by reducing diarrhea and improving tumor response.

Huanglian Jiedu Decoction for treatment of multiple myeloma

“…[ 13 – 15 ] Besides, some reports about mechanism of Huanglian Jiedu Decoction have revealed its multichannel, which includes JAK2/STAT3, TLR4/MyD88 signaling pathway, etc, anti-inflammatory, and anti-cancer effect. [ 11 , 21 – 23 ] After careful literature search, we found there is no quantitative meta-analysis on the treatment of MM by Huanglian Jiedu Decoction so far. It is, therefore, necessary to carry out a study to assess the efficacy, and help to propose the clinical recommendation for MM.…”

Efficient Stool Collection Methods for Evaluating the Diarrhea Score in Mouse Diarrhea Models

“…Researchers using mouse diarrhea models for the first time may therefore encounter difficulties in collecting intact stools and consequently in evaluating the diarrhea score. Moreover, the grading boundaries of various diarrhea scores are ambiguous, adding more difficulties in evaluating the diarrhea score (2,5,6,17,22). This study was intended to be helpful in those cases.…”

“…DI was calculated by multiplying the diarrhea incidence rate (the number of diarrheal feces ÷ the total number of feces) by the mean loose stool grade. Fecal water content (wet weight -dry weight) (12,49) and fecal friability tested by pressing with tweezers were also used to evaluate the stool consistency (1,5).…”

“…It was also difficult to evaluate the diarrhea score on the stool stuck to the bedding chips. Moreover, it was often difficult to determine the exact grade for the parameters employed in evaluating the diarrhea score, because of the overlapping ambiguous boundaries between grades described in many previous studies (2,5,6,17,22).…”

Study on the Fingerprints and Quality Evaluation of Angelica Sinensis Radix by HPLC Coupled With Chemometrics Based on Traditional Decoction Process of ACPTCM

“…Several research on classical prescriptions have been developed. 6 - 15 For instance, Danggui Buxue Tang (DBT), an ancient formula composed of Angelica Sinensis Radix (ASR) and Astragali Radix (AR), first recorded in “Neiwaishang Bianhuo Lun” 16 by Li, Dongyuan in China in AD 1247. In TCM clinics, DBT is prescribed for women to improve their health by raising the “Qi” (vital energy) and nourishing the “Blood” (body circulation), 17 , 18 and thus DBT today is a remedy for menopausal women to promote hematopoiesis, stimulate cardiovascular circulation, prevent osteoporosis, and trigger estrogenic activity.…”