Sijunzi decoction, a classical Chinese herbal formula, improves fatigue symptoms with changes in gut microbiota in chronic fatigue syndrome: A randomized, double-blind, placebo-controlled, multi-center clinical trial.

BACKGROUD: Chronic fatigue syndrome (CFS) severely impact patients' quality of life and lacks well-acknowledged drug therapy. Sijunzi decoction (SJZD), a classical Chinese herbal formula, has been widely used for spleen deficiency syndrome like fatigue in China. However, there is a lack of evidence on the efficacy of SJZD in treating CFS. PURPOSE: To evaluate the efficacy and safety of SJZD for CFS. STUDY DESIGN: A multi-center, double-blinded, randomized controlled trial. METHODS: Participants with definite diagnoses of CFS and spleen deficiency syndrome were randomly assigned in 1:1 ratio to receive SJZD or placebo granules for 2 months. The primary outcome was the change of Chalder fatigue questionnaire (CFQ) scoring after treatment. Other outcomes included changes in short form-36 physical function (SF36-PF) score, spleen deficiency scale score, Euroqol Questionnaire-Visual Analogue Scale (ED-VAS) score, and clinical global impression (CGI) evaluating by corresponding questionnaires. Fecal metagenome sequencing was conducted to explore the potential mechanism of SJZD effect. RESULTS: From June 2020 to July 2021, 105 of 127 participants completed the study at four hospitals in China. After a 2-month treatment, intention-to-treat (ITT) analysis found participants who received SJZD had larger reduction than placebo control (mean change 6.65 [standard deviation (SD) 6.11] points vs. 5.31 [SD 5.19] points; difference 1.34, 95 % confidence interval [CI] -0.65 to 3.33). Per-protocol (PP) analysis reported confirmative results with a significant difference between SJZD and placebo groups (2.24, 95 % CI 0.10 to 4.39). SJZD also significantly improved overall health status compared with placebo in per-protocol population (p = 0.009). No significant difference was found between groups in changes of SF36-PF, spleen deficiency scale scoring, and CGI. Fecal metagenome sequencing and correlation analyses indicated that the beneficial effect of SJZD may be related to the abundance change of Pediococcus acidilactici. No serious adverse event or abnormal laboratory test was found during the whole study. CONCLUSION: Our results indicated that SJZD can improve fatigue symptom and overall health status in patients with CFS under good medication adherence. Potential therapeutic effects may be related to the regulation of gut microbiota. Large-scale trials with longer intervention period are encouraged to further support SJZD's application. CLINICAL TRIAL REGISTRATION: (ID, ISRCTN23930966, URL = https://www.isrctn.com/ISRCTN23930966).

Chinese medicine Phragmites communis (Lu Gen) for acute respiratory tract infections: a systematic review and meta-analysis of randomized controlled trials.

Background: Acute respiratory tract infections (ARTIs) are the most common cause of morbidity and mortality worldwide, with most people experiencing at least one episode per year. Current treatment options are mainly symptomatic therapy. Antivirals, antibiotics, and glucocorticoids are of limited benefit for most infections. Traditional Chinese medicine has shown potential benefits in the treatment of ARTIs. Objective: The objective of this study was to determine the efficacy, effectiveness, and safety of Phragmites communis Trin. (P. communis, a synonym of Phragmites australis (Cav.) Trin. ex Steud) as monotherapy or as part of an herb mixture for ARTIs. Method: Eight databases and two clinical trial registries were searched from inception to 8 February 2023 for randomized controlled trials (RCTs) evaluating any preparation involving P. communis without language restrictions. The Risk of Bias Tool 2.0 was used to assess the risk of bias of the included trials. RevMan 5.3 software was used for data analyses with effects estimated as risk ratios (RRs), mean differences (MDs), or standardized mean differences (SMDs) with 95% confidence intervals (CIs). The online GRADEpro tool was used to assess the certainty of the evidence, if available. Results: Forty-two RCTs involving 6,879 patients with ARTIs were included, with all trials investigating P. communis as part of an herbal mixture. Of the included trials, the majority (38/42) were considered high risk. Compared to the placebo, P. communis preparations improved the cure rate [RR = 1.60, 95% CI (1.13, 2.26)] and fever clearance time [MD = -2.73 h, 95% CI (-4.85, -0.61)]. Compared to usual care alone, P. communis preparations also significantly improved the cure rate [RR = 1.57, 95% CI (1.36, 1.81)] and fever clearance time [SMD = -1.24, 95% CI (-2.37, -0.11)]. P. communis preparations plus usual care compared to usual care alone increased the cure rate [RR = 1.55, 95% CI (1.35, 1.78)], shortened the fever clearance time [MD = -19.31 h, 95% CI (-33.35, -5.27)], and improved FEV1 [ MD = 0.19 L, 95% CI (0.13, 0.26)] and FVC [ MD = 0.16 L, 95% CI (0.03, 0.28)]. Conclusion: Low- or very low-certainty evidence suggests that P. communis preparations may improve the cure rate of ARTIs, shorten the fever clearance time in febrile patients, and improve the pulmonary function of patients with acute exacerbation of chronic obstructive pulmonary disease or chronic bronchitis. However, these findings are inconclusive and need to be confirmed in rigorously designed trials. Systematic review registration: PROSPERO, identifier CRD42021239936.

Therapeutic potential of traditional Chinese medicine in the prevention and treatment of digestive inflammatory cancer transformation: Portulaca oleracea L. as a promising drug.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicine (TCM) has been used for centuries to treat various types of inflammation and tumors of the digestive system. Portulaca oleracea L. (POL), has been used in TCM for thousands of years. The chemical composition of POL is variable and includes flavonoids, alkaloids, terpenoids and organic acids and other classes of natural compounds. Many of these compounds exhibit powerful anti-inflammatory and anti-cancer-transforming effects in the digestive system. AIM OF STUDY: In this review, we focus on the potential therapeutic role of POL in NASH, gastritis and colitis and their associated cancers, with a focus on the pharmacological properties and potential mechanisms of action of the main natural active compounds in POL. METHODS: The information and data on Portulaca oleracea L. and its main active ingredients were collated from various resources like ethnobotanical textbooks and literature databases such as CNKI, VIP (Chinese literature), PubMed, Science Direct, Elsevier and Google Scholar (English literatures), Wiley, Springer, Tailor and Francis, Scopus, Inflibnet. RESULTS: Kaempferol, luteolin, myricetin, quercetin, genistein, EPA, DHA, and melatonin were found to improve NASH and NASH-HCC, while kaempferol, apigenin, luteolin, and quercetin played a therapeutic role in gastritis and gastric cancer. Apigenin, luteolin, myricetin, quercetin, genistein, lupeol, vitamin C and melatonin were found to have therapeutic effects in the treatment of colitis and its associated cancers. The discovery of the beneficial effects of these natural active compounds in POL supports the idea that POL could be a promising novel candidate for the treatment and prevention of inflammation-related cancers of the digestive system. CONCLUSION: The discovery of the beneficial effects of these natural active compounds in POL supports the idea that POL could be a promising novel candidate for the treatment and prevention of inflammation-related cancers of the digestive system. However, clinical data describing the mode of action of the naturally active compounds of POL are still lacking. In addition, pharmacokinetic data for POL compounds, such as changes in drug dose and absorption rates, cannot be extrapolated from animal models and need to be measured in patients in clinical trials. On the one hand, a systematic meta-analysis of the existing publications on TCM containing POL still needs to be carried out. On the other hand, studies on the hepatic and renal toxicity of POL are also needed. Additionally, well-designed preclinical and clinical studies to validate the therapeutic effects of TCM need to be performed, thus hopefully providing a basis for the validation of the clinical benefits of POL.

The Landscape of Gut Microbiota and Its Metabolites: A Key to Understanding the Pathophysiology of Pattern in Chinese Medicine.

Liver Stagnation and Spleen Deficiency (LSSD) is a Chinese Medicine (CM) pattern commonly observed in gastrointestinal (GI) diseases, yet its biological nature remains unknown. This limits the global use of CM medications for treating GI diseases. Recent studies emphasize the role of gut microbiota and their metabolites in the pathogenesis and treatment of LSSD-associated GI diseases. There is increasing evidence supporting that an altered gut microbiome in LSSD patients or animals contributes to GI and extra-intestinal symptoms and affects the effectiveness of CM therapies. The gut microbiota is considered to be an essential component of the biological basis of LSSD. This study aims to provide an overview of existing research findings and gaps for the pathophysiological study of LSSD from the gut microbiota perspective in order to understand the relationship between the CM pattern and disease progression and to optimize CM-based diagnosis, prevention, and therapy.

Targeted metabolomics revealed the mechanisms underlying the role of Liansu capsule in ameliorating functional dyspepsia.

ETHNOPHARMACOLOGICAL RELEVANCE: Liansu capsule could alleviate dyspeptic symptoms; however, the mechanisms underlying its role in treating functional dyspepsia (FD) remain unclear. AIM OF THE STUDY: To elucidate the mechanism underlying the efficacy of Liansu capsule in alleviating FD symptoms. MATERIALS AND METHODS: Thirty-six male mice were randomly divided into the following six groups: control, model, low-strength Liansu, moderate-strength Liansu, high-strength Liansu, and domperidone groups. Small intestine propulsion rate, gastric residual rate and histopathological analysis were performed to evaluate efficacy of Liansu capsule. Levels of interleukin-1ß, interleukin-6, tumor necrosis factor α, phosphorylation of p65, ghrelin and gastrin were verified by real-time quantitative polymerase chain reaction and immunofluorescence assays. Targeted metabolomic analyses, western blotting and immunofluorescence assays were used to explore the mechanism of Liansu capsule in ameliorating FD. RESULTS: The Liansu capsule significantly ameliorated the symptoms of FD, and markedly increased the levels of ghrelin and gastrin. Moreover, Liansu capsule significantly downregulated the levels of the proinflammatory cytokine interleukin-1ß, interleukin-6, tumor necrosis factor α, and inhibited the phosphorylation of p65. Targeted metabolomic analyses showed that Liansu capsule significantly reduced the levels of deoxycholic acid and hyodeoxycholic acid, which were significantly elevated in the model group. Furthermore, these results showed that deoxycholic acid and hyodeoxycholic acid markedly promoted the levels of Takeda G-protein-coupled receptor 5 (TGR5), phosphorylated signal transducer and activator of transcription 3 (STAT3), and Kruppel-like factor 5 (KLF5) in vitro. whereas, Liansu capsule significantly reduced the levels of TGR5, phosphorylated STAT3, and KLF5. CONCLUSION: Our findings indicated that Liansu capsule improved FD by regulating the deoxycholic acid/hyodeoxycholic acid-TGR5-STAT3-KLF5 axis. The findings reveal a novel mechanism underlying the role of Liansu capsule, which may be a promising therapeutic strategy for FD.

Electroacupuncture pretreatment preserves telomerase reverse transcriptase function and alleviates postoperative cognitive dysfunction by suppressing oxidative stress and neuroinflammation in aged mice.

BACKGROUND: Elderly patients often exhibit postoperative cognitive dysfunction (POCD), a postsurgical decline in memory and executive function. Oxidative stress and neuroinflammation, both pathological characteristics of the aged brain, contribute to this decline. This study posits that electroacupuncture (EA) stimulation, an effective antioxidant and anti-inflammatory modality, may enhance telomerase reverse transcriptase (TERT) function, the catalytic subunit of telomerase known for its protective properties against cellular senescence and oxidative damage, to alleviate POCD in aged mice. METHODS: The animal POCD model was created by subjecting aged mice to abdominal surgery, followed by EA pretreatment at the Baihui acupoint (GV20). Postoperative cognitive function was gauged using the Morris water maze (MWM) test. Hippocampal TERT mRNA levels and telomerase activity were determined through qPCR and a Telomerase PCR ELISA kit, respectively. Oxidative stress was assessed through superoxide dismutase (SOD), reactive oxygen species (ROS), and malondialdehyde (MDA) levels. Iba-1 immunostaining determined the quantity of hippocampal microglia. Additionally, western blotting assessed TERT, autophagy markers, and proinflammatory cytokines at the protein level. RESULTS: Abdominal surgery in aged mice significantly decreased telomerase activity and TERT mRNA and protein levels, but increased oxidative stress and neuroinflammation and decreased autophagy in the hippocampus. EA-pretreated mice demonstrated improved postoperative cognitive performance, enhanced telomerase activity, increased TERT protein expression, improved TERT mitochondrial localization, and reduced oxidative damage, autophagy dysfunction, and neuroinflammation. The neuroprotective benefits of EA pretreatment were diminished following TERT knockdown. CONCLUSIONS: Our findings underscore the significance of TERT function preservation in alleviating surgery-induced oxidative stress and neuroinflammation in aged mice. A novel neuroprotective mechanism of EA stimulation is highlighted, whereby modulation of TERT and telomerase activity reduces oxidative damage and neuroinflammation. Consequently, maintaining TERT function via EA treatment could serve as an effective strategy for managing POCD in elderly patients.

Application of metabolomics in irritable bowel syndrome in recent 5 years.

Irritable bowel syndrome (IBS) is one of the most common functional gastrointestinal disorders worldwide, characterized by chronic abdominal pain or discomfort and altered bowel habits. To date, the exact pathogenesis of IBS remains elusive, but is clearly multifactorial, including environmental and host factors. However, the management of patients with IBS is challenging and the current diagnostic and therapeutic modalities have unsatisfactory outcomes. Therefore, it is important to develop more effective methods to diagnose IBS early. Metabolomics studies the metabolites most closely related to patient characteristics, which can provide useful clinical biomarkers that can be applied to IBS and may open up new diagnostic approaches. Traditional Chinese medicine (TCM) can play a role in improving symptoms and protecting target organs, but its mechanism needs to be studied in depth. In this review, based on PubMed/MEDLINE and other databases, we searched metabolomics studies related to IBS in the past 5 years, including those related to clinical studies and animal studies, as well as literatures on TCM interventions in IBS, to provide an updated overview of the application of metabolomics to the diagnosis and treatment of IBS and the improvement of IBS by TCM.

Exploring the mechanism of Jianpi Huatan recipe in protecting hepatocellular carcinoma based on network pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Jianpi Huatan Recipe (JPHTR) is an effective prescription for delaying progression of hepatocellular carcinoma (HCC) provided by Longhua Hospital affiliated to Shanghai University of traditional Chinese Medicine, and it is consisted of nine traditional Chinese drugs, but the protective mechanism of JPHTR against HCC progression is unclear. AIM OF THE STUDY: To study the mechanism of JPHTR preventing the progression of HCC based on the network pharmacology. MATERIALS AND METHODS: The chemical component and potential gene targets of JPHTR and the important gene targets of HCC were obtained by retrieving traditional Chinese medicine network pharmacology analysis system (TCMNPAS) database. The data obtained from the database are used to construct the drugs-chemical component-targets network and protein-protein interaction network by using Cytoscape software and STRING database. The potential targets of JPHTR and HCC targets were imported into TCMNPAS-related modules in order to obtain the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment pathways. Finally, we used HCC rat model to verify the vital signaling pathways predicted by network pharmacology. RESULTS: A total of 197 potential compounds and 721 potential targets of JPHTR and 611 important gene targets of HCC were obtained. Through the experiment in vivo, it was found that JPHTR can reduce the serum levels of alanine aminotransferase, aspartate aminotransferase and alkaline phosphatase, reduce the lipid droplets and inflammatory injury of liver tissue, and reduce the mRNA expression of Interleukin-6 (Il-6), Janus tyrosine Kinase2 (Jak2) and Forkhead box O3 (Foxo3) in FOXO pathway in the liver, thus delaying the development of HCC. CONCLUSION: Through network pharmacology and rat experiments, it is preliminarily confirmed that JPHTR may delay the progression of HCC by regulating the expression of Il-6/Jak2/Foxo3 in FOXO signal pathway, which is expected to be a new therapeutic target for the protection of HCC.

Sijunzi decoction granules in the prevention and treatment of recurrence of colorectal adenoma: Study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

Background: The recurrence of colorectal adenomas (CRAs) after endoscopy predisposes patients to a risk of colorectal cancer. Guided by the traditional Chinese medicine (TCM), patients with colorectal diseases usually manifest with spleen deficiency syndrome (SDS) and are treated with Sijunzi decoction (SJZD). Therefore, this trial aims to explore the efficacy and safety of SJZD in the prevention and treatment of CRAs recurrence. Methods: SJZD on prevention and treatment of CRAs recurrence after resection: a multicenter, randomized, double-blind, placebo-controlled trial was designed. Patients who undergo polypectomy of CRAs will be recruited and randomized into a SJZD group and a placebo group in a 1:1 ratio. The intervention phase will be 12 months. The follow-up period will last 24 months. The primary outcome is the CRA recurrence rate after intervention. The secondary outcomes include the CRA recurrence rate at the second year post-polypectomy, the pathological type of adenoma and the alterations in SDS scores after intervention. Discussion: Previous clinical practice has observed the sound effect of SJZD in the context of gastrointestinal diseases. A number of experiments have also validated the active components in SJZD. This trial aims to provide tangible evidence for the usage of SJZD, hoping to reduce the recurrence of CRAs.

Qinggan Huoxue Recipe attenuates Alcoholic Liver Disease by suppressing PI3K/AKT signaling pathway based on network pharmacology.

Qinggan Huoxue Recipe (QGHXR) is originated from Xiao Chaihu Decotion. Many experimental studies have confirmed that QGHXR can significantly alleviate the symptoms of alcoholic liver disease (ALD), but the detailed mechanism is still unclear. Using traditional Chinese medicine network pharmacology analysis system database and animal experiments, we found that 180 potentially chemical compositions and 618 potential targets were screened from the prescription, which shared 133 signal pathways with ALD. Through animal experiments, it was found that QGHXR could reduce the liver total cholesterol (TC), serum TC, alanine aminotransferase, aspartate aminotransferase of ALD mice, reduce the lipid droplets and inflammatory injury of liver tissue. Meanwhile, it can also increase PTEN, decrease PI3K and AKT mRNA levels. In this study, we obtained the targets and pathways of QGHXR in the treatment of ALD, and preliminatively verified that QGHXR may improve ALD through PTEN/PI3K/AKT signaling pathway.

The Western and Chinese exercise training for blood pressure reduction among hypertensive patients: An overview of systematic reviews.

Hypertension remains the world's leading cause of premature death. Interventions such as exercise, diet modification, and pharmacological therapy remain the mainstay of hypertension treatment. Numerous systematic reviews and meta-analyses demonstrated the effectiveness of western exercises, such as aerobic exercise and resistance exercise, in reducing blood pressure in hypertensive patients. There is recently emerging evidence of blood pressure reduction with Chinese exercises, such as Tai Chi, Baduanjin, and Qigong. The current overview of systematic reviews aims to evaluate the quality and descriptively summarize the evidence for the effectiveness of western and Chinese exercises for hypertension management. Thirty-nine systematic reviews were included in this overview, with 15 of those being on Chinese exercise. Evidence suggests that exercise training, regardless of Western or Chinese exercise, generally reduced both systolic and diastolic blood pressure. High-intensity intermittent training did not further reduce blood pressure when compared to moderate-intensity continuous training. Conflicting results on the effectiveness of blood pressure reduction when comparing Chinese and Western exercise training were observed. This suggests the comparable effectiveness of Chinese exercise training, in particularly Tai Chi, to general or aerobic exercise training in terms of blood pressure reduction. The Chinese exercise modality and intensity may be more suitable for the middle-aged and elderly population.

Lingguizhugan decoction improves non-alcoholic steatohepatitis partially by modulating gut microbiota and correlated metabolites.

Background: Lingguizhugan decoction is a traditional Chinese medicine prescription that has been used to improve non-alcoholic fatty liver disease and its progressive form, non-alcoholic steatohepatitis (NASH). However, the anti-NASH effects and underlying mechanisms of Lingguizhugan decoction remain unclear. Methods: Male Sprague-Dawley rats were fed a methionine- and choline-deficient (MCD) diet to induce NASH, and then given Lingguizhugan decoction orally for four weeks. NASH indexes were evaluated by histopathological analysis and biochemical parameters including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), liver triglycerides (TG), etc. Fecal samples of rats were subjected to profile the changes of gut microbiota and metabolites using 16S rRNA sequencing and ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS). Bioinformatics was used to identify Lingguizhugan decoction reversed candidates, and Spearman's correlation analysis was performed to uncover the relationship among gut microbiota, fecal metabolites, and NASH indexes. Results: Four-week Lingguizhugan decoction treatment ameliorated MCD diet-induced NASH features, as evidenced by improved hepatic steatosis and inflammation, as well as decreased serum AST and ALT levels. Besides, Lingguizhugan decoction partially restored the changes in gut microbial community composition in NASH rats. Meanwhile, the relative abundance of 26 genera was significantly changed in NASH rats, and 11 genera (such as odoribacter, Ruminococcus_1, Ruminococcaceae_UCG-004, etc.) were identified as significantly reversed by Lingguizhugan decoction. Additionally, a total of 99 metabolites were significantly altered in NASH rats, and 57 metabolites (such as TDCA, Glutamic acid, Isocaproic acid, etc.) enriched in different pathways were reversed by Lingguizhugan decoction. Furthermore, Spearman's correlation analyses revealed that most of the 57 metabolites were significantly correlated with 11 genera and NASH indexes. Conclusion: Lingguizhugan decoction may exert protective effects on NASH partially by modulating gut microbiota and correlated metabolites.

First Report of Leaf Spot Caused by Lasiodiplodia theobromae on Kadsura coccinea in China.

Kadsura coccinea (Lem.) A. C. Smith is an evergreen liana widely cultivated in China for its economic importance in traditional medicine. Many phytochemical studies on the stems and roots of K. coccinea have shown a variety of biological activities, such as anti-hepatitis, anti-HIV, and anti-tumor (Yang et al. 2020). In July 2021, symptoms of leaf spot were observed in a plantation of K. coccinea in Longan (23°03´N, 107°54´E), Guangxi province, China. The incidence of this disease was 36%, and severity varies from approximately 20 to 40% of leaf surface coverage. Symptoms began as small brown spots that expanded into irregular to nearly flower-shaped lesions. To isolate the pathogen, leaves with spots were collected, sterilized with 75% ethanol for 15 s followed by 2% sodium hypochlorite for 120 s, rinsed three times in sterilized distilled water, cut into 5 × 5 mm pieces, and placed onto potato dextrose agar (PDA) plates. The plates were kept in an incubator at 26°C in the dark for at least 2 days. A total of 27 fungal colonies of similar morphology out of 30 pieces of infected tissues were isolated. Four representative isolates (HBB1 to HBB4) were selected to study for further characterization. Fungal colonies were initially grayish-white and then turned greenish-gray on PDA. The black pycnidium and immature conidia appeared over PDA plates after 18 days. The immature conidia were colorless and transparent, elliptical, and had a single-cell structure. After 5 days, the immature conidia gradually become black and develop into mature conidia. The mature conidia were dark brown and two-celled with longitudinal striations, 20.41-29.93 × 12.42-17.19 µm (average 26.07×14.51 µm; n = 100). For DNA-based identification, the internal transcribed spacer (ITS) region, translation elongation factor 1 alpha (EF1-α), and ß-tubulin (TUB) genes of the isolates were amplified and sequenced using the primers ITS1/ITS4 (White et al. 1990), EF1-728F/EF1-986R (Carbone and Kohn 1999), and Bt2a/Bt2b (Glass and Donaldson 1995), respectively. Sequences were submitted to GenBank (Accession nos. MW045412 to MW045415 for ITS, MW065559 to MW065562 for EF1-α, and MW065555 to MW065558 for TUB). A phylogenetic analysis was conducted using the Maximum Likelihood method on concatenated sequences of the three genes, which showed that the four Chinese isolates from K. coccinea were clustered with reference isolates of Lasiodiplodia theobromae including the ex-neotype CBS 164.96. Pathogenicity tests were performed on young, fully expanded leaves of 2-year seedlings. A 10 µL conidial suspension (1×106 conidia/mL) was inoculated on each wound on the left-half leaf and a 10 µL sterile water was inoculated on each wound on the right-half leaf (control). Each treatment was repeated three times. Inoculated leaves were wrapped in plastic bags for 5 days and plants were maintained in a growth chamber at 27°C, 85% relative humidity. Brown leaf spots appeared 5 to 6 days after inoculation, whereas the control leaves treated with sterile water showed no symptoms. All re-isolations from spots produced colonies with the same morphological characters as L. theobromae, completing Koch's postulates. To our knowledge, this is the first report of L. theobromae causing leaf spot on K. coccinea in China and worldwide. Severe leaf disease caused by L. theobromae threatens K. coccinea production. The disease threatens K. coccinea growth, and effective control measures should be identified to reduce losses.

Application of metabolomics in the diagnosis of non-alcoholic fatty liver disease and the treatment of traditional Chinese medicine.

Non-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease around the world, and it often coexists with insulin resistance-related diseases including obesity, diabetes, hyperlipidemia, and hypertension, which seriously threatens human health. Better prevention and treatment strategies are required to improve the impact of NAFLD. Although needle biopsy is an effective tool for diagnosing NAFLD, this method is invasive and difficult to perform. Therefore, it is very important to develop more efficient approaches for the early diagnosis of NAFLD. Traditional Chinese medicine (TCM) can play a certain role in improving symptoms and protecting target organs, and its mechanism of action needs to be further studied. Metabolomics, the study of all metabolites that is thought to be most closely associated with the patients' characters, can provide useful clinically biomarkers that can be applied to NAFLD and may open up new methods for diagnosis. Metabolomics technology is consistent with the overall concept of TCM, and it can also be used as a potential mechanism to explain the effects of TCM by measuring biomarkers by metabolomics. Based on PubMed/MEDLINE and other databases, this paper retrieved relevant literature NAFLD and TCM intervention in NAFLD using metabolomics technology in the past 5 years were searched, and the specific metabolites associated with the development of NAFLD and the potential mechanism of Chinese medicine on improving symptoms were summarized.

Modified acupuncture therapy, long-term acupoint stimulation versus sham control for weight control: a multicenter, randomized controlled trial.

Objective: Long-term acupoint stimulation (LAS), also called embedding acupuncture, is a modified acupuncture technique. The preliminary results have demonstrated its efficacy in body-weight control. However, the low quality of available trials limited its application. This study aimed to evaluate the efficacy and safety of LAS in body-weight control by using a randomized, parallel, sham-controlled clinical trial design. Methods: This was a randomized, single-blind, sham-controlled clinical trial including 84 adult participants (18-60 years) with a body mass index (BMI) of ≥ 24 kg/m2 conducted in three general hospitals in Shanghai, China. Participants were equally assigned to receive LAS or sham LAS (SLAS) once per 10 days, eight times in total. After completion, an additional intervention with a 3-month follow-up period was set to examine the continued effect of LAS. The primary outcome was the change in body weight from baseline to treatment endpoint within the intention-to-treat (ITT) analysis. Secondary outcomes contained changes in waist-to-hip ratio (WHR), lipid metabolism, and visceral and subcutaneous adipose tissues. Results: From 14 May 2018 to 03 November 2019, 84 participants out of 201 screened individuals met the eligibility criteria, were randomized, and were analyzed (42 participants in each group). From baseline to treatment endpoint, the body-weight reduction in the LAS group was significantly larger than in the sham control (net difference: 1.57 kg, 95% CI: 0.29-2.86, p = 0.012). The superior weight reduction effect persisted in the follow-up period (net difference: 3.20 kg, 95% CI: 1.17-5.21, p = 0.001). LAS therapy also showed improvement in triglyceride and subcutaneous adipose tissue (SAT) compared with sham control. One participant in the LAS group reported a slightly uncomfortable and tingling sensation after the additional intervention. No other adverse events (AEs) were documented. Conclusion: LAS, a modified acupuncture technique, is safe and effective in body-weight control. It could be used as an alternative choice to classical acupuncture for obesity management. Clinical Trial Registration: [www.chictr.org.cn], identifier [ChiCTR1800015498].

Gynostemma pentaphyllum polysaccharides ameliorate non-alcoholic steatohepatitis in mice associated with gut microbiota and the TLR2/NLRP3 pathway.

Recent studies have revealed the pivotal role of gut microbiota in the progress of liver diseases including non-alcoholic steatohepatitis (NASH). Many natural herbs, such as Gynostemma pentaphyllum (GP), have been extensively applied in the prevention of NASH, while the bioactive components and underlying mechanism remain unclear. The aim of this study was to investigate whether the polysaccharides of GP (GPP) have a protective effect on NASH and to explore the potential mechanism underlying these effects. C57BL/6 male mice were fed with a methionine-choline-deficient (MCD) diet for 4 weeks to induce NASH and administered daily oral gavage of sodium carboxymethylcellulose (CMC-Na), low dose of GPP (LGPP), high dose of GPP (HGPP), and polyene phosphatidylcholine capsules (PPC), compared with the methionine-choline-sufficient (MCS) group. Our results showed that the symptoms of hepatic steatosis, hepatocyte ballooning, liver fibrosis, and oxidative stress could be partially recovered through the intervention of GPP with a dose-dependent effect. Furthermore, gut microbiome sequencing revealed that HGPP altered the composition of gut microbiota, mainly characterized by the enrichment of genera including Akkermansia, Lactobacillus, and A2. Moreover, hepatic transcriptome analysis indicated that the anti-inflammatory effect of HGPP might be associated with toll-like receptor (TLR) and nod-like receptor (NLR) signaling pathways. HGPP could inhibit the expression of TLR2 and downregulate the expression of the NLRP3 inflammasome, as well as the pro-inflammatory cytokine tumor necrosis factor (TNF)-α and interleukin (IL)-1ß. In summary, GPP could ameliorate NASH possibly mediated via the modulation of gut microbiota and the TLR2/NLRP3 signaling pathway, indicating that GPP could be tested as a prebiotic agent in the prevention of NASH.

Appraisal of treatment outcomes in integrative medicine using metabonomics: Taking non-alcoholic fatty liver disease with spleen deficiency syndrome as an example.

OBJECTIVE: Appraisal of treatment outcomes in integrative medicine is a challenge due to a gap between the concepts of Western medicine (WM) disease and traditional Chinese medicine (TCM) syndrome. This study presents an approach for the appraisal of integrative medicine that is based on targeted metabolomics. We use non-alcoholic fatty liver disease with spleen deficiency syndrome as a test case. METHODS: A patient-reported outcome (PRO) scale was developed based on literature review, Delphi consensus survey, and reliability and validity test, to quantitatively evaluate spleen deficiency syndrome. Then, a metabonomic foundation for the treatment of non-alcoholic fatty liver disease with spleen deficiency syndrome was identified via a longitudinal interventional trial and targeted metabolomics. Finally, an integrated appraisal model was established by identifying metabolites that responded in the treatment of WM disease and TCM syndrome as positive outcomes and using other aspects of the metabonomic foundation as independent variables. RESULTS: Ten symptoms and signs were included in the spleen deficiency PRO scale. The internal reliability, content validity, discriminative validity and structural validity of the scale were all qualified. Based on treatment responses to treatments for WM disease (homeostasis model assessment of insulin resistance) or TCM syndrome (spleen deficiency PRO scale score) from a previous randomized controlled trial, two cohorts comprised of 30 participants each were established for targeted metabolomics detection. Twenty-five metabolites were found to be involved in successful treatment outcomes to both WM and TCM, following quantitative comparison and multivariate analysis. Finally, the model of the integrated appraisal system was exploratively established using binary logistic regression; it included 9 core metabolites and had the prediction probability of 83.3%. CONCLUSION: This study presented a new and comprehensive research route for integrative appraisal of treatment outcomes for WM disease and TCM syndrome. Critical research techniques used in this research included the development of a TCM syndrome assessment tool, a longitudinal interventional trial with verified TCM treatment, identification of homogeneous metabolites, and statistical modeling.

First Report of Leaf Spot Caused by Phyllosticta capitalensis on Illicium difengpi in China.

Illicium difengpi B. N. Chang et al., a shrub with aromatic odor in the Illicium genus, is extensively used as a medicinal plant in China. In June of 2020, a leaf spot on I. difengpi with incidence of about sixty percent was observed in a field located in Guilin (25°4'40"N; 110°18'21"E), Guangxi Province, China. Initial leaf symptoms were round spots with gray centers, surrounded by yellow halos. The spots gradually spread and merged. Six samples of symptomatic leaves were collected from six diseased plants, and they were surface disinfested before isolation. Potato dextrose agar (PDA) was used to culture pathogens. Successively, pure cultures were obtained by transferring hyphal tips to new PDA plates. A total of 10 isolates were obtained from the affected leaves. Two single-spore isolates (GX-1 and GX-2) were obtained and confirmed to be identical based on morphological characteristics. The representative isolate GX-2 was selected for further study on morphological and molecular characteristics. The colony of isolate GX-2 was about 4 cm in diameter on a PDA plate in 5 days, dark green with a granular surface, and irregular white edge. Conidia were hyaline, unicellular, oval, narrow at the end with a single apical appendage, and 8.2 to 13.8 × 3.7 to 7.2 µm (n = 50). Spermatia were hyaline, bacilliform with swollen ends, 3.8 to 8.9 × 1.3 to 1.9 µm (n = 50). Morphological characteristics of isolate GX-2 were consistent with the description of Phyllosticta capitalensis (Wikee et al. 2013). The internal transcribed spacer (ITS) region, translation elongation factor 1-α (tef1-α), glyceraldehyde-3-phosphate dehydrogenase (GPDH) and actin (ACT) were amplified using primers ITS1/ITS4, EF-728F/EF-986R, Gpd1-LM/Gpd2-LM and ACT-512F/ACT-783R, respectively (Wikee et al. 2013). Sequences were deposited in GenBank with accession numbers OL505439 for ITS, OL539429 for ACT, OL539430 for tef1-α and OL539431 for GPDH. BLAST analysis in GenBank showed that these sequences were 99 to 100% similar to the corresponding ITS (MT649668), ACT (MN958710), tef1-α (MN958711) and GPDH (KU716077) sequences of P. capitalensis. Also, the phylogenetic tree based on genes of ITS, tef1-α, GPDH and ACT by the maximum likelihood method showed that isolate GX-2 clustered together with P. capitalensis. The pathogenicity tests were carried out on a healthy 3 year-old plant in the greenhouse with 80% relative humidity at 25 °C. Four sterilized leaves were wounded with a needle and inoculated with 20 µL spore suspension (1 × 106 spores/ml). Another four sterilized leaves were inoculated with 20 µL sterile water as a control. All plants were incubated in a chamber with 98% relative humidity at 25 ± 1°C. After 12 days, disease symptoms similar to the field were observed on leaves, whereas control plants remained healthy. P. capitalensis was successfully reisolated only from the inoculated leaves and identified based on morphological characters. P. capitalensis caused leaf spots on various host plants around the world (Wikee et al. 2013), including on tea plants in China (Cheng et al. 2019) and oil palm in Malaysia (Nasehi et al. 2020), but it has not been reported on I. difengpi. Thus, this is the first report of P. capitalensis causing leaf spot on I. difengpi. This study will provide an important reference for the control of the disease. The epidemiology of this disease should be investigated in further research.

The improvement of nonalcoholic steatohepatitis by Poria cocos polysaccharides associated with gut microbiota and NF-κB/CCL3/CCR1 axis.

BACKGROUND: Nonalcoholic steatohepatitis (NASH) has been linked to inflammation induced by intestinal microbiota. Poria cocos polysaccharides (PCP) possesses anti-inflammation and immunomodulation functions; however, its preventive effects against NASH and potential mechanisms need to be explored. METHODS: The composition of PCP was determined using ion chromatography. C57BL/6 mice were administered the methionine and choline deficient (MCD) diet for 4 weeks to establish the NASH model or methionine-choline-sufficient (MCS) diet to serve as the control. Mice were assigned to the MCS group, MCD group, low-dose PCP (LP) group, and high-dose PCP (HP) group, and were administered the corresponding medications via gavage. Serum biochemical index analysis and liver histopathology examination were performed to verify the successful establishment of NASH model and to evaluate the efficacy of PCP. The composition of intestinal bacteria was profiled through 16S rRNA gene sequencing. Hepatic RNA sequencing (RNA-Seq) was performed to explore the potential mechanisms, which were further confirmed using qPCR, western blot, and immunohistochemistry. RESULTS: PCP consists of glucose, galactose, mannose, D-glucosamine hydrochloride, xylose, arabinose, and fucose. PCP could significantly alleviate symptoms of NASH, including histological liver damage, impaired hepatic function, and increased oxidative stress. Meanwhile, HP could reshape the composition of intestinal bacteria by significantly increasing the relative abundance of Faecalibaculum and decreasing the level of endotoxin load derived from gut bacteria. PCP could also downregulate the expression of pathways associated with immunity and inflammation, including the chemokine signaling pathway, Toll-like receptor signaling pathway, and NF-kappa B signaling pathway. The expression levels of CCL3 and CCR1 (involved in the chemokine signaling pathway), Tlr4, Cd11b, and NF-κb (involved in the NF-kappa B signaling pathway), and Tnf-α (involved in the TNF signaling pathway) were significantly reduced in the HP group compared to the MCD group. CONCLUSIONS: PCP could prevent the development of NASH, which may be associated with the modulation of intestinal microbiota and the downregulation of the NF-κB/CCL3/CCR1 axis.