Qualitative identification of lonicerae japonicae flos in traditional chinese medicine using metabarcoding combined with specific mini-barcodes.

BACKGROUND: Lonicerae japonicae flos, also known as Jinyinhua (JYH), is an important component of traditional Chinese patent medicine (TCPM) products. However, the potential for adulteration and substitution with low-quality materials highlights the need for a reliable and sensitive approach to identify the species composition of TCPM products for consumer safety. METHODS AND RESULTS: We used universal ITS2 primers to amplify TCPMs containing JYH. However, the results were inconclusive, as only one operational taxonomic unit (OTU) was identified as Lonicera sp., which could not be identified at the species level. To confirm the species identification of Lonicera sp. in TCPM, we developed a short mini-barcode primer based on the psbA-trnH region, which, in combination with DNA metabarcoding technology, allowed for qualitative and quantitative analysis of artificially mixed samples. We applied the mini-barcode to distinguish TCPMs containing JYH and demonstrated its relatively accurate quantitative ability in identifying two Lonicera species. CONCLUSIONS: Our study presents a method for qualitative and quantitative identification of JYH, providing a promising application of DNA metabarcoding technology in the quality control of TCPM products.

[Research progress in original species identification in industry chain of Rhei Radix et Rhizoma].

Rhei Radix et Rhizoma is a kind of commonly used Chinese medicinal materials. Due to the overharvesting, the wild resource is endangering. Large market demand caused severely adulterant of commercial Rhei Radix et Rhizoma medicinal materials and decoction pieces. This manuscript reviewed the advances of the original species authentication in the industrial chain of Rhei Radix et Rhizoma during the latest decade, including characteristics and microscopic features, phytochemical analysis on anthraquinones, and molecular authentication based on DNA barcoding. Accordingly, an original species authentication route for the industrial chain of Rhei Radix et Rhizoma was summarized:(1)the identification of seeds and seedlings by DNA barcoding;(2) the selection of high variable sites based on the chloroplast genome;(3)biomonitoring of the Rhei Radix et Rhizoma medicinal materials and decoction pieces by two-dimensional DNA barcode;(4)traceability of Chinese patent medicines by third-generation sequencing. In conclusion, the combination of molecular identification and traditional identification methods provides a new idea for the identification of the original species of Rhei Radix et Rhizoma in the industrial chain and a essential guidance for the research of drug safety and efficacy of Rhei Radix et Rhizoma.

Traditional Chinese patent medicine for prophylactic treatment of migraine: a meta-analysis of randomized, double-blind, placebo-controlled trials.

BACKGROUND AND PURPOSE: A large number of traditional Chinese patent medicines (TCPMs) are widely used to treat migraine in China. However, it is uncertain whether there is robust evidence on the effects of TCPMs for migraine. A meta-analysis of randomized, double-blind, placebo-controlled trials was performed to evaluate the efficacy and safety of TCPMs in patients with migraine. METHODS: Comprehensive searches were conducted on the Medline database, Cochrane Library, the China National Knowledge Infrastructure database, the Chinese Biomedical Literature database and the Wanfang database up to December 2013. Summary estimates, including 95% confidence intervals (CIs), were calculated for frequency of migraine attacks, response rate and headache intensity. RESULTS: A total of seven trials including 582 participants with migraine met the selection criteria. TCPM was significantly more likely to reduce the frequency of migraine attacks compared with placebo (standardized mean difference -0.54; 95% CI -0.72, -0.36; P < 0.001). TCPM was associated with an improvement of response rate compared with placebo (summary relative risk 4.63, 95% CI 2.74, 7.80, P < 0.001; therapeutic gain 24.1%; number needed to treat 4.1). Headache intensity was attenuated by TCPM compared with placebo (standardized mean difference -1.33; 95% CI -1.79, -0.87; P < 0.001). The adverse events of TCPM were no different from those of placebo. CONCLUSION: TCPMs are effective and well tolerated in the prophylactic treatment of migraine.

Efficacy and safety of Yangxue Qingnao Granules in treatment of migraine: A systematic review and meta-analysis.

BACKGROUND: Yangxue Qingnao Granules (YXQN) is a Chinese patent medicine that has been commonly used in the clinical treatment of migraine. AIM: To assess the efficacy and safety of YXQN alone for the treatment of migraine. METHODS: We searched 10 databases to identify relevant randomized controlled trials (RCTs) published before September 2022. Two review authors independently searched and screened the literature, extracted the data, and assessed the methodological quality of the studies using criteria from ROB 2.0, and analyzed the data using Review Manager 5.4 software. RESULTS: A total of 12 RCTs including 767 participants with migraine met the selection criteria. We divided these studies into comparisons of YXQN with placebo, routine treatment drugs, and other Chinese patent medicines. The meta-analysis showed the following: (1) Efficacy: The YXQN group outperformed the placebo group [relative risk (RR) = 0.29, 95% confidence interval (95%CI): 0.15-0.43, P < 0.00001], routine treatment group (RR = 0.18, 95%CI: 0.09-0.27, P < 0.0001), and Chinese patent medicine group (RR = 0.27, 95%CI: 0.13-0.41, P < 0.001); (2) frequency of headache: There was a significant difference between YXQN vs placebo [mean difference (MD) = -1.25, 95%CI: -1.60 to -0.90, P < 0.00001], routine treatment drugs (MD = -0.85, 95%CI: -1.15 to -0.56, P < 0.00001), and Chinese patent medicine (MD = -0.91, 95%CI: -1.35 to -0.46, P < 0.0001); (3) headache duration: We found great heterogeneity between studies, with no differences between YXQN and placebo (MD = -0.61, 95%CI: -1.53 to -0.31, P = 0.19) and routine treatment drugs (MD = -0.22, 95%CI: -0.89 to 0.46, P < 0.53). YXQN was more effective than other Chinese patent medicines in reducing headache duration (MD = -1.24, 95%CI: -1.70 to -0.77, P < 0.00001); and (4) headache severity: There was no significant difference between YXQN vs placebo (MD = -1.67, 95%CI: -3.52 to 0.19, P = 0.08), routine treatment drugs (MD = -0.53, 95%CI: -2.02 to 0.96, P = 0.68), and other Chinese patent medicines (MD = -0.49, 95%CI: -2.83 to 1.85, P = 0.68). Mild gastrointestinal adverse reactions were reported in three cases. CONCLUSION: This study revealed that YXQN is effective and safe for treatment of migraine.

DNA barcoding combined with high-resolution melting analysis to discriminate rhubarb species and its traditional Chinese patent medicines.

Introduction: Rhubarb is a frequently used and beneficial traditional Chinese medicine. Wild resources of these plants are constantly being depleted, meaning that rhubarb products have been subjected to an unparalleled level of adulteration. Consequentially, reliable technology is urgently required to verify the authenticity of rhubarb raw materials and commercial botanical drugs. Methods: In this study, the barcode-DNA high-resolution melting (Bar-HRM) method was applied to characterize 63 rhubarb samples (five Polygonaceae species: Rheum tanguticum, Rh. palmatum, Rh. officinale, Rumex japonicus and Ru. sp.) and distinguish the rhubarb contents of 24 traditional Chinese patent medicine (TCPM) samples. Three markers, namely ITS2, rbcL and psbA-trnH, were tested to assess the candidate DNA barcodes for their effectiveness in distinguishing rhubarb from its adulterants. A segment from ITS2 was selected as the most suitable mini-barcode to identify the botanical drug rhubarb in TCPMs. Then, rhubarbs and TCPM samples were subjected to HRM analysis based on the ITS2 barcode. Results: Among the tested barcoding loci, ITS2 displayed abundant sites of variation and was effective in identifying Polygonaceae species and their botanical origins. HRM analysis based on the ITS2 mini-barcode region successfully distinguished the authenticity of five Polygonaceae species and eight batches of TCPMs. Of the 18 TCPM samples, 66.7 % (12 samples) were identified as containing Rh. tanguticum or Rh. officinale. However, 33.3 % were shown to consist of adulterants. Conclusions: These results demonstrated that DNA barcoding combined with HRM is a specific, suitable and powerful approach for identifying rhubarb species and TCPMs, which is crucial to guaranteeing the security of medicinal plants being traded internationally.

In-vitro and In-vivo Identification, Absorbtion and Metabolism Network Analysis of Filifolium sibiricum Flavonoids Dropping Pill by UHPLC-Q-TOF-MS.

BACKGROUND: Filifolium sibiricum flavonoids dropping pill (FSFp), a unique Chinese Filifolii sibirici herba extract preparation, has the potential as an alternative therapy against S. aureus infection (SA) and antiinfection. However, its chemical composition and in vivo metabolism characteristics remain unknown, which limits its clinical application. METHODS: Here, we aimed to understand the in vitro and in vivo material basis of FSFp. Ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS) was used to identify chemicals in FSFp as well as its phase I and phase II reaction metabolites in plasma, urine and feces. RESULTS: A total of 38 chemicals were characterized in FSFp, including 22 flavonoids, 10 organic acids, 3 chromones, 1 aromatic ketone, 1 coumarin, and 1 ligan. After analysis of the drugged bio-samples, a total of 21 compounds were found in urine, and 16 of them were found in feces, but only one was found in plasma. In addition, 56 FSFp-related metabolites were characterized, of which 56 were in urine, 4 in feces, and 8 in plasma. CONCLUSION: This is the first comprehensive research of FSFp on chemical constituents and metabolic profiles. It was expected that this study would offer reliable support for further investigation of FSFp.

Treatment options of traditional Chinese patent medicines for dyslipidemia in patients with prediabetes: A systematic review and network meta-analysis.

Objective: To compare the clinical efficacy and safety of SIX Traditional Chinese Patent Medicines (TCPM) recommended by guidelines in improving lipids for patients with prediabetes by network meta-analysis. Methods: Randomized controlled trials of 6 TCPM in the treatment of prediabetes were searched systematically in various databases. After extracting effective data, the risk of bias was assessed using Review Manager 5.3 and Cochrane Collaboration Systems Evaluator's Manual. Network meta-analysis was performed using STATA 15.0 based on the frequency statistical model. The effect size and credibility of the evidence for the intervention were summarized based on a minimal contextualized framework. Results: A total of 27 studies involving 2,227 patients were included. Compared with lifestyle modification (LM), Shenqi + LM [SMD -0.49 (95% CI: -0.85, -0.12)] and Jinqi + LM [SMD -0.44 (95% CI: -0.81, -0.06)] showed statistically significant effect in lowering TG, Shenqi + LM [SMD -0.51 (95%CI: -0.86, -0.17)] and Jinqi + LM [SMD -0.44 (95%CI: -0.80, -0.08)] in lowering TC, Jinlida + LM [SMD -0.31 (95%CI: -0.59, -0.04)] in lowering LDL-C, Shenqi + LM [SMD 0.29 (95%CI: 0.06, 0.51)] and Jinqi + LM [SMD 0.16 (95%CI: 0.01, 0.31)] in increasing HDL-C. Conclusion: For patients with prediabetes, Traditional Chinese patent medicine Jinqi and Shenqi combined with lifestyle modification were associated with a significant reduction in TG and TC, while Shenqi + LM was among the most effective. Jinlida + LM was among the least effective. Systematic Review Registration: https://clinicaltrials.gov/, identifier PROSPERO(CRD42021279332).

Comparative efficacy of 6 traditional Chinese patent medicines combined with lifestyle modification in patients with prediabetes: A network meta-analysis.

OBJECTIVE: To evaluate the efficacy of 6 Traditional Chinese patent medicines combined with lifestyle modification in the treatment of prediabetes with network meta-analysis. METHOD: The randomized controlled trials (RCTs) of Shen qi jiang tang capsule/granule (Shenqi), Tian mai xiao ke tablet (Tianmai), Tian qi capsule (Tianqi), Jin qi jiang tang tablet (Jinqi), Jin li da granule (Jinlida), Tang mai kang granule (Tangmaikang) in the treatment of prediabetes in PubMed, Web of Science, The Cochrane Library, EMbase, China Knowledge Network (CNKI), WanFang and Weipu databases were searched. Three reviewers independently conducted the screening, extracted the data and assessed methodological quality. Data analysis was performed using Rev Man 5.3 and STATA 15.0 software. RESULTS: A total of 50 RCTs, including 4594 patients, were included. The addition of Shenqi (OR 0.19 [95 %CI: 0.07, 0.52]) and Jinqi (OR 0.32 [95 %CI: 0.15, 0.71]) to existing lifestyle modification resulted in significant lower incidence rate of DM compared with none/placebo added to lifestyle modification. The addition of Jinlida (SMD -0.41% [95 %CI:-0.81, -0.01]) and Tangmaikang (SMD -0.83%[95 %CI: -1.46,-0.20]) resulted in significant additional HbA1c reductions compared with none/placebo added to lifestyle modification. The addition of all CTPMs except Tianqi resulted in significant additional FBG reductions and the addition of Shenqi (SMD -1.96[95 %CI: -3.64, -0.28]) resulted in significant additional PBG reductions. CONCLUSION: For patients with prediabetes, Shenqi + LM was among the most effective in reducing the incidence of diabetes for patients with prediabetes, while Jinlida + LM was among the least effective. Jinqi + LM and Tianqi + LM might be among the most effective, while western oral drugs + LM, Tianmai + LM, Tangmaikang + LM and Placebo + LM might be among the least effective. In addition, Tangmaikang + LM and Jinlida + LM might be among the most effective in reducing HbA1c, while Tianmai + LM, Tangmaikang + LM, Shenqi + LM, Jinlida + LM and Jinqi + LM might be among the most effective in reducing FPG for patients with prediabetes. Yet direct comparison and further investigation to explore mechanisms are warranted.

TaqMan Probe-Based Quantitative Real-Time PCR to Detect Panax notoginseng in Traditional Chinese Patent Medicines.

Background: There has been global concern about the safety and accuracy of traditional Chinese patent medicines (TCPMs). Panax notoginseng, also known as sanqi, is an important constituent of TCPMs. However, identifying the species contained in TCPMs is challenging due to the presence of multiple ingredients and the use of various preparation processes. Objective: To detect P. notoginseng in TCPMs. Methods: A TaqMan probe-based qPCR assay was constructed and validated with DNA extracted from P. notoginseng and adulterants. In total, 75 samples derived from 25 batches of TCPMs were tested using the constructed qPCR method. Results: A TaqMan probe-based qPCR assay targeting P. notoginseng was established. The constructed qPCR assay could specifically discriminate P. notoginseng from Panax ginseng, Panax quinquefolium and Curcuma aromatica Salisb. cv. Wenyujin. The sensitivity study showed that the detectable DNA template concentration of P. notoginseng for this qPCR assay was 0.001 ng/µl. All 75 samples from TCPMs were confirmed to contain P. notoginseng by the qPCR assay. Conclusions: The qPCR method can accurately identify P. notoginseng in TCPMs and is promising as a powerful tool for quality control and market regulation.

Traditional Chinese patent medicine for bile reflux gastritis: a systematic review and network meta-analysis.

BACKGROUND: Traditional Chinese Patent Medicine (TCPM) is widely used in the treatment of bile reflux gastritis (BRG). However, there is still a lack of research evaluating the efficacy of specific drugs. Thus, we conducted a reticulated meta-analysis to compare the efficacy of TCPMs in the treatment of BRG. METHODS: We searched the China National Knowledge Infrastructure (CNKI), PubMed, Web of Science, and the Wanfang, and Embase databases, as of February 2021, for publications on the treatment of BRG with Chinese patent medicines in randomized controlled trials (RCTs). The main outcome indicator was the effective rate. The secondary outcome indicators were recurrence rate, traditional Chinese medicine (TCM) symptom score, and gastroscopic mucosal score. The Cochrane bias risk assessment tool was used to evaluate the research quality, and RevMan software (5.2) and Stata software (15.0) were used for the network meta-analysis. RESULTS: A total of 24 studies were included in the meta-analysis. In total, 2,417 patients were included in the meta-analysis, comprising 1,222 patients in the treatment group and 1,195 patients in the control group. The results of the network meta-analysis showed that Weiyankang capsules combined with hydrotalcite had the best effect in the treatment of bile reflux among the 14 interventions. Among the 5 studies that reported recurrence rates, patients administered Shugan Hewei pills had the lowest recurrence rate. A direct comparison showed that TCPMs or TCPMs combined with Western medicines had certain advantages in improving the scores of traditional Chinese medicine symptoms and mucosal scores under gastroscopy. DISCUSSION: Among all the Chinese patent medicines examined, Weiyankang capsules combined with hydrotalcite appeared to be the best choice for the treatment of BRG. However, due to limitations related to the quantity and quality of the research, more high-quality research needs to be conducted in the future to gather additional evidence. TRIAL REGISTRATION: The protocol of this network meta-analysis was registered in PROSPERO with ID CRD42021247873.

Traditional Chinese Patent Medicine for Treating Impaired Glucose Tolerance: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION/AIM: To assess the effectiveness and safety of Traditional Chinese patent medicines (TCPMs) for managing impaired glucose tolerance (IGT). METHODS: Seven databases were searched to identify eligible trials published from incepting to May 1, 2016. Randomized controlled trials (RCTs) involving TCPM for IGT with a minimum follow-up duration of 6 months were included for analysis. Data extraction and quality assessment were performed by two reviewers independently. Data synthesis was analyzed using Review Manager 5.3 software. Subgroup analysis was carried out to assess the robustness of results of meta-analysis. RESULTS: Eighteen trials with a total of 3172 participants met the inclusion criteria. The methodological quality of the RCTs was variable. Comparing with receiving lifestyle modification (LM) alone, TCPM plus LM was significantly better at reducing the incidence of diabetes (risk ratio [RR] 0.45; 95% confidence interval [CI] 0.36-0.57, p < 0.00001) and normalizing the blood glucose (RR 0.72; 95% CI 0.64-0.82, p < 0.00001). TCPM plus LM was superior in decreasing the levels of 2hPG, body mass index (BMI), fasting insulin, and 2 h insulin compared with LM alone (2hPG: mean difference [MD] -1.13; 95% CI -1.68 to -0.58, p < 0.0001; BMI: MD -0.42; 95% CI -0.71 to -0.14, p = 0.004; fasting insulin: MD -2.44; 95% CI -3.79 to -1.09, p = 0.0004; and 2 h insulin: MD -8.26; 95% CI -8.47 to -8.05, p < 0.00001). Compared with placebo plus LM, TCPM plus LM was superior in reducing diabetes (RR 0.54; 95% CI 0.42-0.69, p < 0.00001) and normalizing blood glucose (RR 0.55; 95% CI 0.41-0.73, p < 0.00001; the interventions were also associated with a decline in the two-hour postprandial blood glucose (2hPG) levels (MD -1.45; 95% CI -2.11 to -0.79, p < 0.0001) and BMI levels (MD -1.12; 95% CI -2.00 to -0.24, p < 0.0001). There were no significant differences in adverse events between two groups. Subgroup analysis found no significant difference in overall effects among all study characteristics, indicating that the overall effects were stable. CONCLUSIONS: The study indicated that TCPM combined with moderate lifestyle modification had significant effect on IGT. Further studies are needed to provide more reliable evidence. The PROSPERO registration is No. CRD42016039312.