Metabolic stimulation-elicited transcriptional responses and biosynthesis of acylated triterpenoids precursors in the medicinal plant Helicteres angustifolia.

BACKGROUND: Helicteres angustifolia has long been used in Chinese traditional medicine. It has multiple pharmacological benefits, including anti-inflammatory, anti-viral and anti-tumor effects. Its main active chemicals include betulinic acid, oleanolic acid, helicteric acid, helicterilic acid, and other triterpenoid saponins. It is worth noting that some acylated triterpenoids, such as helicteric acid and helicterilic acid, are characteristic components of Helicteres and are relatively rare among other plants. However, reliance on natural plants as the only sources of these is not enough to meet the market requirement. Therefore, the engineering of its metabolic pathway is of high research value for enhancing the production of secondary metabolites. Unfortunately, there are few studies on the biosynthetic pathways of triterpenoids in H. angustifolia, hindering its further investigation. RESULTS: Here, the RNAs of different groups treated by metabolic stimulation were sequenced with an Illumina high-throughput sequencing platform, resulting in 121 gigabases of data. A total of 424,824 unigenes were obtained after the trimming and assembly of the raw data, and 22,430 unigenes were determined to be differentially expressed. In addition, three oxidosqualene cyclases (OSCs) and four Cytochrome P450 (CYP450s) were screened, of which one OSC (HaOSC1) and one CYP450 (HaCYPi3) achieved functional verification, suggesting that they could catalyze the production of lupeol and oleanolic acid, respectively. CONCLUSION: In general, the transcriptomic data of H. angustifolia was first reported and analyzed to study functional genes. Three OSCs, four CYP450s and three acyltransferases were screened out as candidate genes to perform further functional verification, which demonstrated that HaOSC1 and HaCYPi3 encode for lupeol synthase and ß-amyrin oxidase, which produce corresponding products of lupeol and oleanolic acid, respectively. Their successful identification revealed pivotal steps in the biosynthesis of acylated triterpenoids precursors, which laid a foundation for further study on acylated triterpenoids. Overall, these results shed light on the regulation of acylated triterpenoids biosynthesis.

Efficacy and safety of Qingre-Chushi therapies in active ulcerative colitis: A network meta-analysis.

BACKGROUND: Ulcerative colitis (UC) is a chronic inflammatory disease with an increasing incidence in the world. Qingre-Chushi therapies (QC) can alleviate clinical symptoms. Therefore, a network meta-analysis was conducted to systematically evaluate the efficacy and safety of QC in the treatment of active UC patients. METHODS: 7 databases were screened and relevant randomized controlled trials were selected. The tools of Cochrane Handbook and the GRADE system were conducted to assess the quality of outcomes. Pooled risk ratio or standard mean difference was calculated with 95% credible interval for outcomes measurement using the random-effects model. The surface under the cumulative ranking curve (SUCRA) was performed to rank the treatments. The larger SUCRA scores, the more effective interventions. RESULTS: A total of 3560 articles were identified and 21 studies including 1829 participants were included for further analysis. Totally, 9 therapies regimens were compared: oral mesalazine, mesalazine enema, mesalazine suppository, oral mesalazine + mesalazine enema, oral QC, oral QC + oral mesalazine, QC enema, oral QC + QC enema, and oral mesalazine + QC enema. Based on the SUCRA plot, oral QC + oral mesalazine was the best treatment in inducing clinical response; oral QC + QC enema had the best efficacy in the improvement of Mayo scores and alleviating abdominal pain; oral mesalazine + mesalazine enema was the optimal therapy in the endoscopic improvement and reducing diarrhea; QC enema + oral mesalazine was the best option in preventing bloody stool. CONCLUSION: This study confirmed the efficacy and safety of QC in treating active UC and suggested that the combination of oral medications with topical can achieve more benefits.

Pharmacological treatments of Chinese herbal medicine for irritable bowel syndrome in adults: A network meta-analysis of randomized controlled trials.

INTRODUCTION: Plenty of clinical studies have suggested the value of Chinese herbal medicine (CHM) for patients with irritable bowel syndrome (IBS), but their efficacy and safety have not been systematically concluded yet. This article aimed to compare and rank the therapeutic effect and safety of CHM with routine pharmacotherapies and placebo in the treatment of IBS. METHODS: Randomized controlled trials regarding CHM to treat IBS were searched in six databases from inception to Jan 31, 2020. A network meta-analysis was conducted to analyze the data of included publications. The quality assessment was assessed by Cochrane Handbook and GRADEpro software. The risk ratio was calculated for dichotomous outcomes while the standardized mean difference was used for continuous variables with 95% credible intervals. A Funnel plot was performed to evaluate publication bias. The surface under the cumulative ranking curve was conducted to rank the included interventions. Data were analyzed with STATA 15.0 and Review Manager 5.3. RESULT: 3194 records were searched, and 28 eligible trials involving 3323 patients ere identified. Compared with conventional therapies and placebo, Jianpi-Chushi therapy showed significant improvement in adequate relief and IBS symptom severity scale; Shugan-Jianpi therapy showed the best efficacy in relieving the abdominal pain and abdominal distension; Wenshen-Jianpi therapy had a better effect on avoiding adverse effects and improving stool character. CONCLUSION: This study confirmed that CHM could be beneficial for patients with IBS in relieving their clinical symptoms and should be recommended as alternative therapies. The quality of evidence in this study based on the GRADE system was "low".