A comprehensive review of bupleuri radix and its bioactive components： with a major focus on treating chronic liver diseases.

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleuri Radix (BR) has been recognized as an essential herbal medicine for relieving liver depression for thousands of years. Contemporary research has provided compelling evidence of its pharmacological effects, including anti-inflammatory, immunomodulatory, metabolic regulation, and anticancer properties, positioning it as a promising treatment option for various liver diseases. Hepatitis, steatohepatitis, cirrhosis, and liver cancer are among the prevalent and impactful liver diseases worldwide. However, there remains a lack of comprehensive systematic reviews that explore the prescription, bio-active components, and underlying mechanisms of BR in treating liver diseases. AIM OF THE REVIEW: To summarize the BR classical Chinese medical prescription and ingredients in treating liver diseases and their mechanisms to inform reference for further development and research. MATERIALS AND METHODS: Literature in the last three decades of BR and its classical Chinese medical prescription and ingredients were collated and summarized by searching PubMed, Wiley, Springer, Google Scholar, Web of Science, CNKI, etc. RESULTS: BR and its classical prescriptions, such as Xiao Chai Hu decoction, Da Chai Hu decoction, Si Ni San, and Chai Hu Shu Gan San, have been utilized for centuries as effective therapies for liver diseases, including hepatitis, steatohepatitis, cirrhosis, and liver cancer. BR is a rich source of active ingredients, such as saikosaponins, polysaccharides, flavonoids, sterols, organic acids, and so on. These bioactive compounds exhibit a wide range of beneficial effects, including anti-inflammatory, antioxidant, immunomodulatory, and lipid metabolism regulation. However, it is important to acknowledge that BR and its constituents can also possess hepatotoxicity, which is associated with cytochrome P450 (CYP450) enzymes and oxidative stress. Therefore, caution should be exercised when using BR in therapeutic applications to ensure the safe and appropriate utilization of its potential benefits while minimizing any potential risks. CONCLUSIONS: To sum up, BR, its compounds, and its based traditional Chinese medicine are effective in liver diseases through multiple targets, multiple pathways, and multiple effects. Advances in pharmacological and toxicological investigations of BR and its bio-active components in the future will provide further contributions to the discovery of novel therapeutics for liver diseases.

Efficacy and safety of Shouhui Tongbian Capsules in the treatment of constipation: A systematic review and meta-analysis.

BACKGROUND: Constipation is a common gastrointestinal disorder, which has seriously affected the quality of people's daily life. Traditional Chinese Medicine (TCM) therapy takes syndrome differentiation and treatment as the theoretical guidance with certain advantages in treating constipation with the holistic approach. However, there are few studies on the treatment of constipation with Shouhui Tongbian Capsules (SHTB). PURPOSE: This study was aimed to evaluate the clinical effect and safety of SHTB in the treatment of constipation and provide evidence-based references for clinical application. STUDY DESIGN: A systematic review and meta-analysis of existing literature on SHTB for treating constipation. METHODS: Chinese databases (China Network Knowledge Infrastructure, Wan Fang Database and Chinese Scientific Journal Database) and English databases (PubMed, EmBase and the Cochrane Library) were thoroughly investigated through screening randomized controlled trials on SHTB for constipation from the establishment of all databases to September 26, 2022. Data extraction and quality evaluation were performed on the literature that met the inclusion criteria and a meta-analysis was performed for selected data using Review Manager 5.4, ROB 2.0 and Stata 17.0. RESULTS: A total of 14 RCTs (randomized controlled trial) including 1310 participants were included in the analysis. The results showed that the test group was superior to the control group in improving the total effective rate and curative effect, clinical symptom score, gastrointestinal peptide index and reducing adverse reactions and recurrence rate. The specific results were as follows: ① The total effective rate increased significantly (RR = 1.24, 95% CI [1.18, 1.30], Z = 8.25, p< 0.00001); ② The clinical symptom indexs, including the difficulty of defecation [SMD = -1.28, 95% CI (-1.44, -1.12), Z = 15.65, p< 0.00001], the frequency of spontaneous defecation [SMD = 1.28, 95% CI (1.01, 1.54), Z = 9.52, p< 0.00001], defecation interval [SMD = -1.47, 95% CI (-1.68, -1.26), Z = 13.79, p < 0.00001], incomplete defecation [SMD = -1.34, 95% CI (-1.57, -1.11), Z = 11.42, p < 0.00001], duration of defecation [SMD = -2.02, 95% CI (-2.39, -1.65), Z = 10.73, p < 0.00001], stool characteristics [SMD = -2.30, 95% CI (-2.60, -1.99), Z = 14.72, p< 0.00001] and TCM main syndrome scores [SMD = -1.25, 95% CI (-1.46, -1.05), Z = 11.79, p< 0.00001] increased observably; ③ The gastrointestinal peptide hormone indexs, including MTL Level [SMD = 0.43, 95% CI (0.24, 0.62), Z = 4.44, p < 0.00001] and SP Level [RR =0.57, 95% CI (0.37, 0.87), Z = 2.61, p = 0.009] were improved obviously; ④ The incidence of adverse reactions (RR = 0.57, 95% CI [0.37, 0.87], Z = 2.61, p = 0.009) and recurrence rate (RR = 0.31, 95% CI [0.18, 0.54], Z = 4.28, P <0.001) reduced significantly. Sensitivity analysis showed that there was no significant change in all outcome indicators, which suggested that the results of meta-analysis were relatively stable. Funnel plot and Egger test results showed that the literature included in the study might have publication bias. CONCLUSION: SHTB can be used to treat functional constipation, especially elderly functional constipation, constipation caused by tumor chemotherapy and disease concomitant constipation. The optimal dosage of SHTB was 0.70 g (2 capsules) each time, 3 times a day, for 28 days. Combined with basic treatment, lactose oral solution, mosaic or castor oil could improve the total effective rate, clinical symptom indicators, gastrointestinal peptide hormone indicators and reduce adverse reaction rate of patients. However, due to the limitations of the included clinical trials, high-quality clinical trials with long follow ups are needed to evaluate the effectiveness and safety of SHTB in treating different types of constipation.

Si-Ni-SAN ameliorates obesity through AKT/AMPK/HSL pathway-mediated lipolysis: Network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Si-Ni-San (SNS) is a famous Chinese herbal formula used in China for thousands of years. It has clinical effects on a variety of lipid metabolism disorders, but the ameliorating effects of SNS on obesity and underlying mechanisms remained poorly elucidated. AIM OF THE STUDY: This study aims to explore the therapeutic effect and mechanism of SNS on obesity from multiple perspectives in vitro and in vivo. MATERIALS AND METHODS: The high-fat diet (HFD)-induced obesity mouse model was established to evaluate the effect of SNS. Then network pharmacologic methods were performed to predict underlying mechanisms, and the core pathways were verified in animal and cell studies. RESULTS: Our results demonstrated that SNS significantly reduced body weight, body fat content, white adipose tissue (WAT) expansion in obese mice, and lipid accumulation in primary mouse embryonic fibroblasts (MEFs) cells. Network pharmacologic analysis identified 66 potential therapeutic targets, and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of these genes revealed that the most important signaling pathway includes AMP-activated protein kinase (AMPK) signaling pathway, regulation of lipolysis in adipocytes, lipid and atherosclerosis. Western blot assay confirmed that SNS activated hormone-sensitive triglyceride lipase (HSL) and adipose triglyceride lipase (ATGL) activity and promoted lipolysis through AMPK signaling pathway. CONCLUSION: The results confirmed that SNS improves lipid accumulation through AKT/AMPK/HSL axis mediated lipolysis, which opens a new option for clinical treatment of obesity and associated complications.

Enantiomer metabolism of acephate and its metabolite methamidophos in in vitro tea (Camellia sinensis L.) systems: Comparison between cell suspensions and excised tissues.

Enantioselective metabolism of chiral pesticide in plants is very important. In vitro system has become an effective means to study the metabolism of pesticides in plants, but the study on the metabolism of chiral pesticides has not been reported. This work compared the enantiomer metabolic behavior of acephate and its metabolite methamidophos between tea cell suspensions and excised tea stem with leaves. (±)-Acephate could be absorbed and transferred well to top leaves by the cut end of excised stem after 24 h. (±)-Methamidophos was derived from the metabolism of (±)-acephate in tea plants at 3-5% in leaves and 2-3% in stems at 216 h. The content of (+)-methamidophos was 1.5 times higher than that of (-)-methamidophos in excised leaves. Though both (±)-acephate and (±)-methamidophos could be metabolized well by cell suspension, (±)-acephate and (±)-methamidophos was non-enantioselectively metabolized in cell suspension. It was shown that using the excised tea stem with leaves for chiral pesticide metabolism studies was much closer to intact plant than cell suspensions. This result also established an effective and easily available in vitro metabolic model for the study of enantioselective metabolism of chiral contaminants from environment.

Mapping spatio-temporal dynamics of main water parameters and understanding their relationships with driving factors using GF-1 images in a clear reservoir.

Due to eutrophication and water quality deterioration in clear reservoirs, it is necessary to monitor and manage the main water parameters: concentration of total phosphorus (CTP), chemical oxygen demand (CCOD), chlorophyll-a (CChla), total suspended matter (CTSM), and Secchi disk depth (SDD). Five random forest (RF) models are developed to estimate these parameters in Xin'anjiang Reservoir, which is a clear drinking water resource in Zhejiang, China. Then, the spatio-temporal distributions of the parameters over 7 years (2013-2019) are mapped using GaoFen-1 (GF-1) images and the relationships with driving factors are analyzed. Our study demonstrates that the parameters' distributions exhibited a significant spatio-temporal difference in Xin'anjiang Reservoir. Spatially, relatively high CTP, CCOD, CChla, and CTSM but low SDD appear in riverine areas, showing strong evidence of impact from the incoming rivers. Temporally, CChla and CTSM reached high values in summer and winter, whereas SDD and CTP were higher in the summer and autumn, respectively. In contrast, no significant seasonal variations of CCOD could be observed. This may be why CCOD is not sensitive to hydrological or meteorological factors. However, precipitation had a significant impact on CChla, CTP, SDD, and CTSM in riverine areas, though these parameters were less sensitive to meteorological factors. Moreover, the geomorphology of the reservoir and anthropogenic interference (e.g., tourism activities) also have a significant impact on the water quality parameters. This study demonstrates that coupling long-term GF-1 images and RF models could provide strong evidence and new insights to understand long-term dynamics in water quality and therefore support the development of corresponding management strategies for freshwater reservoirs.

Identification of Bupleurum (Apiaceae) seeds by allele-specific PCR based on ITS sequences.

The traditional Chinese medicine Bupleuri radix (chaihu) is the dried roots of Bupleurum chinense and Bupleurum scorzonerifolium and many adulterants exist because of the differences in traditional understanding, medication habits and seed resources. Therefore, rapid and accurate identification methods for Bupleurum (Apiaceae) seeds are required. We analyzed the internal transcribed spacer (ITS) sequences of five common Bupleurum species to detect variations in them, including B. chinense, B. scorzonerifolium, B. marginatum var. stenophyllum, B. falcatum and B. smithii var.parvifolium. Based on single nucleotide polymorphisms (SNPs) in the ITS region, we designed five specific primer pairs and used these primers in an allele-specific PCR technique to establish a robust molecular identification method. The neighbor-joining (NJ) tree of ITS sequences showed that five Bupleurum species formed their own monophyly. Five specific primer pairs were designed and integrated into a specific PCR master mix and cycling conditions. The primer pair of BCF/R8 for B. chinense could amplify a specific identification band of 429 bp and the minimum detection limit of the 5 g mixture was about 5%; BSF/R11 for B. scorzonerifolium could amplify a specific 464 bp band and the minimum detection limit was about 5%; BMSF/R1 for B. marginatum var. stenophyllum could amplify a specific 344 bp band and the minimum detection limit was about 1%; BFF/R7 for B. falcatum could amplify a specific 137 bp band and the minimum detection limit was about 1%; BSPF/R1 for B. smithii var. parvifolium could amplify a specific 390 bp band. Subsequent analysis proved the reliable accuracy and good practicability of the five specific identification primers, indicating that the allele-specific primer PCR identification method can quickly identify Bupleurum seeds. The method elaborated in this study has the advantages of simple operation, good accuracy and high efficiency.

Comparison of the Metabolic Behaviors of Six Systemic Insecticides in a Newly Established Cell Suspension Culture Derived from Tea ( Camellia sinensis L.) Leaves.

The use of an in vitro cell suspension to study insecticide metabolism is a simpler strategy compared to using intact plants, especially for a difficult matrix such as tea. In this study, a sterile tea leaf callus was inoculated into B5 liquid media with 2,4-dichlorophenoxyacetic acid (2,4-D, 1.0 mg L-1) and Kinetin (KT, 0.1 mg L-1). After 3-4 subcultures (28 days each), a good cell suspension was established. Utilizing these cultures, the metabolic behaviors of six insecticides, including two organophosphates (dimethoate, omethoate) and four neonicotinoids (thiamethoxam, imidacloprid, acetamiprid, and imidaclothiz) were compared. The results showed that thiamethoxam, dimethoate, and omethoate were easily metabolized by tea cells, with degradation ratios after 75 days of 55.3%, 90.4%, and 100%, respectively. Seven metabolites of thiamethoxan and two metabolites of dimethoate were found in treated cell cultures using mass-spectrometry, compared to only two metabolites for thiamethoxam and one for dimethoate in treated intact plants.

Ca2+-Induced Rigidity Change of the Myosin VIIa IQ Motif-Single α Helix Lever Arm Extension.

Several unconventional myosins contain a highly charged single α helix (SAH) immediately following the calmodulin (CaM) binding IQ motifs, functioning to extend lever arms of these myosins. How such SAH is connected to the IQ motifs and whether the conformation of the IQ motifs-SAH segments are regulated by Ca2+ fluctuations are not known. Here, we demonstrate by solving its crystal structure that the predicted SAH of myosin VIIa (Myo7a) forms a stable SAH. The structure of Myo7a IQ5-SAH segment in complex with apo-CaM reveals that the SAH sequence can extend the length of the Myo7a lever arm. Although Ca2+-CaM remains bound to IQ5-SAH, the Ca2+-induced CaM binding mode change softens the conformation of the IQ5-SAH junction, revealing a Ca2+-induced lever arm flexibility change for Myo7a. We further demonstrate that the last IQ motif of several other myosins also binds to both apo- and Ca2+-CaM, suggesting a common Ca2+-induced conformational regulation mechanism.