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Background: Increasing global interest in natural therapies has led to a rise in the use of herbal medicines for managing various ailments. However, concerns about scientific evaluation have prompted a study aiming to assess the study design of herbal medicine clinical trials. This study aimed to provide a descriptive overview of the study design, characteristics, and methodologies of contemporary herbal medicine clinical trials., Materials and Methods: The study reviewed herbal medicine clinical trials published between 2019 and 2022 in five electronic databases: PubMed, Embase, Web of Sciences, Scopus, and the Cochrane Library. Data extraction included study characteristics, intervention details, study design, outcome measures, trial phases, blinding, and other relevant information, with descriptive analyses presented. The term 'herbal medicines' in this study refers to herbs, herbal materials, preparations, and finished products containing active ingredients from plant parts or their combinations., Results: Out of the initially identified 5,918 records, 1,517 articles were eligible for inclusion in the study. The majority of herbal medicine clinical trials were conducted in Asian countries, covering a range of diseases. A randomized, double-blind, parallel design with a 1:1 allocation ratio was frequently employed, along with the common use of placebos across all trial phases. Capsules were the most common dosage form. The median number of human participants varied across trial phases, ranging from 50 in Phase 1 to 240 in Phase 4., Conclusions: The analysis observed that herbal medicine clinical trials employed randomized, double-blind, parallel designs, and the widespread use of placebo. Our observations provided valuable insights into the evolving landscape of herbal medicine clinical trials., (© 2024. The Author(s).)

Infertility is one of the significant global issues that affects approximately 15-17 % of couples worldwide, with around 50 % of cases being attributed to female infertility factors. The exploration of herbal extracts and their effects on female infertility has been limited, particularly regarding the underlying mechanisms beyond hormonal and oxidative stress influences. In this study, the herbal medicines with potential effects such as antioxidative properties, enhancement of insulin sensitivity, and modulation of the hypothalamic-pituitary-gonadal axis have been reviewed. Several herbal extracts were found to exhibit significant antioxidant properties and demonstrate phytoestrogenic effects on reproductive factors and hormonal levels. Antioxidants are essential in mitigating oxidative stress by neutralizing free radicals, which in turn helps to lower insulin resistance, total cholesterol, fat accumulation, and the proliferation of cancerous cells. Furthermore, this review highlights that certain parts of specific plants are rich in polyphenolic compounds, including isoflavones and flavonoids, along with other advantageous substances that support women's reproductive health. These compounds not only modulate female endocrine systems but also alleviate menopausal symptoms and effectively address a range of reproductive disorders, such as polycystic ovary syndrome (PCOS), premature ovarian failure (POF), endometriosis, hyperprolactinemia, and hypothalamic dysfunction. Turning to the other side, the plants and herbal extracts with suppressive effects on female fertility have been reviewed. These findings indicated that herbal extracts could be exploited to develop natural products as supplements for supporting the female reproductive system., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Ethnopharmacological Relevance: Premature ovarian insufficiency (POI) refers to a dramatic decrease in the number and/or quality of oocytes in the ovaries before the age of 40 years, and is a key cause of female infertility. The prevalence of POI has been increasing annually and tends to be younger. Researches on the etiology of POI and related pathogenesis are still very limited. Herbal medicine can treat many gynecological diseases. And herbal medicine is effective in reproductive health care such as infertility. In recent years, it has been found that immune modulation by cytokines (CK) can prevent or intervene in POI, and herbal medicine can treat POI by regulating CK to improve ovarian function and fertility., Aim of the Study: This review presents an overview of the molecular mechanisms of regulation of POI related CK, and reports the therapeutic effect of herbal medicine on POI including herbal medicine formulas, single herbal medicine, herbal medicine active components and acupuncture. This review provides theoretical support for clinical prevention and treatment of POI, and provides new ideas for researches on herbal medicine treatment of POI., Materials and Methods: We performed a collection of relevant scientific articles from different scientific databases regarding the therapeutic effect of herbal medicine on POI by regulating CK, including PubMed, Web of Science, Wanfang Database, CNKI and other publication resources. The search terms used in this review include, 'premature ovarian insufficiency', 'premature ovarian failure (POF)', 'infertility', 'herbal medicine', 'acupuncture', 'cytokine', 'interleukin (IL)', 'tumor necrosis factor-α (TNF-α)', 'interferon-γ (IFN-γ)', 'transforming growth factor-β (TGF-β)', 'vascular endothelial growth factor (VEGF)', 'immune' and 'inflammation'. This review summarized and analyzed the therapeutic effect of herbal medicine according to the existing experimental and clinical researches., Results: The results showed that herbal medicine treats POI through CK (including ILs, TNF-α, INF-γ, VEGF, TGF-β and others) and related signaling pathways, which regulates reproductive hormones disorder, reduces ovarian inflammatory damage, oxidative stress, apoptosis and follicular atresia, improves ovarian pathological damage and ovarian reserve function., Conclusions: This review enriches the theory of POI treatments based on herbal medicine by regulating CK. The specific mechanisms of action and clinical researches on the treatment of POI by herbal medicine should be strengthened in order to promote the application of herbal medicine in the clinic and provide new ideas and better choices for the treatment of POI., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Feeding intolerance (FI) refers to frequent feeding disruptions, that can adversely affect the growth, nutritional status, and long-term neurodevelopmental outcomes of preterm infants (born at 37 ≤ weeks of gestation). This review evaluated the efficacy of herbal medicine (HM) for FI compared to conventional treatments., Methods: An extensive search across 11 databases was conducted, including English, Chinese, and Korean databases, from August 1 to December 7, 2023. Our inclusion criteria were randomized clinical trials (RCTs) that compared the efficacy of HM with conventional treatments against conventional treatments alone. Statistical analyses involved calculating the mean difference (MD), standardized mean difference (SMD), and risk ratio (RR) with a 95% confidence interval (CI), and assessing the bias risk (RoB 2) using Review Manager Version 5.4 software. The quality of evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) rating system., Results: The meta-analysis showed that combined HM treatments exhibited superior outcomes compared to conventional treatments alone. The time to achieve full enteral feeding (n = 638, random effects MD: -2.91, 95% CI: -4.13 to -1.69), duration of FI (n = 366, fixed effects MD: -1.58, 95% CI: -2.01 to -1.16), and total effective rate (n = 774, random effects RR: 1.26, 95% CI: 1.11 to 1.42) improved with HM. Mild adverse events, such as diarrhea and increased defecation frequency, occurred in 4.17% of the HM combined group, compared to 1.42% in the conventional treatment group., Conclusions: The findings suggest that combining HM with conventional treatments could be more effective for FI, suggesting HM as an early intervention for FI in preterm infants. Further research on the efficacy and safety of HM in preterm infants is necessary.

Anemophilous weeds from the Asteraceae family are highly allergenic and represent a significant source of aeroallergens in late summer and autumn. Ragweed and mugwort pollen allergies have become a significant health burden in Europe. Some people with respiratory allergies to weed pollen may also suffer hypersensitivity reactions to herbal medicines obtained from certain cross-reactive plants in the Compositae family, such as chamomile, marigold, and purple coneflower. General physicians, ear, nose, and throat (ENT) specialists, and pulmonologists need to be familiar with the diagnostic tests used by allergists in clinical practice to support accurate diagnosis in such patients. Allergists must also be aware of the suggestions of the European Medicines Agency (EMA)'s Herbal Medicinal Products Committee and the broad spectrum of herbal therapies to educate their patients about potential risks.

Novel biomaterials are becoming more crucial in treating human diseases. However, many materials require complex artificial modifications and synthesis, leading to potential difficulties in preparation, side effects, and clinical translation. Recently, significant progress has been achieved in terms of direct self-assembly of natural products from herbal medicine (NPHM), an important source for novel medications, resulting in a wide range of bioactive supramolecular materials including gels, and nanoparticles. The NPHM-based supramolecular bioactive materials are produced from renewable resources, are simple to prepare, and have demonstrated multi-functionality including slow-release, smart-responsive release, and especially possess powerful biological effects to treat various diseases. In this review, NPHM-based supramolecular bioactive materials have been revealed as an emerging, revolutionary, and promising strategy. The development, advantages, and limitations of NPHM, as well as the advantageous position of NPHM-based materials, are first reviewed. Subsequently, a systematic and comprehensive analysis of the self-assembly strategies specific to seven major classes of NPHM is highlighted. Insights into the influence of NPHM structural features on the formation of supramolecular materials are also provided. Finally, the drivers and preparations are summarized, emphasizing the biomedical applications, future scientific challenges, and opportunities, with the hope of igniting inspiration for future research and applications., (© 2024 The Author(s). Advanced Science published by Wiley‐VCH GmbH.)

Introduction: Herbal medicine has seen remarkable growth in consumption over the past few years. Community pharmacists are health care professionals who have an important role in the dispensing and counselling of these products. The aim of this study was to evaluate perceptions, professional practices and knowledge about herbal medicine among community pharmacists in Tenerife (Canary Islands, Spain)., Method: A descriptive cross-sectional study was conducted in community pharmacies in Tenerife using a questionnaire that included demographic data, perceptions, professional practices and knowledge of herbal medicine. Data from 610 community pharmacists was analyzed using SPSS 26.0 software program., Results: Most of the responders had a positive attitude towards herbal medicine, considering its products useful (80.9%), safe (64.2%) and those sold in pharmacies of high quality and standardized (84.6%). They thought that these products should only be sold in pharmacies (78.0%) and that it was their responsibility to provide information about them (95.5%). However, only 32.1% believed they are well prepared to provide herbal pharmaceutical care services and 36.1% that there are reliable and easily accessible sources of information. Moreover, 60.7% considered lack of training a barrier to recommending herbal medicinal products, being interested in updating their knowledge on it (96.9%)., Conclusion: This study showed that community pharmacists have a positive perception of herbal medicines, considering them beneficial and safe. However, participants requested reliable sources of information, easy access, and more training to dispense, counsel, and safely label these products. Education and training programs in herbal medicine are needed to enhance their ability to provide herbal pharmaceutical care., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ethnopharmacological Relevance: The only known copy of Sejfer derech ejc ha-chajim, an anonymous old print, is stored in the Austrian National Library in Vienna. It was written in the Yiddish Ashkenazi language and printed in 1613. The author, a Jewish physician, resided or lived in the Polish-Lithuanian Commonwealth. This rare book, although it was printed over 400 years ago, has not yet been systematically assessed in the ethnomedical context of those times., Aim of the Study: A quantitative assessment of the botanical drugs and kinds of healthy diets described in The Guide is presented to recognise the medicinal, diachronic, and botanical outlines of this peculiar rarum., Materials and Methods: To investigate various recipes describing the use of medicinal plants of Jewish culture in the former Polish-Lithuanian Commonwealth, the content of The Guide was analysed. All therapeutic uses of herbal medicines and nutritional recommendations for health were obtained by reviewing the Polish translation of the rare medical handbook. For each plant usage revealed in the text, we noted: Scientific, Common and Yiddish name of the taxon, Plant family, Part of the plant or substance used, Administration, Preparation, Primary pathology, Broad use, and Inferred pathology (ICD-11 and ICPC-3)., Results: Among the 161 recipes, 58 plant taxa and 361 use records were recorded. Additionally, 127 mixtures with 68 plant taxa and 183 use mixture records were noted. 22 diet recipes with 19 plant taxa were also found. These data constitute three separate analyses, according to the intention of the author of The Guide. Formulations using Apiaceae were recommended primarily for gastroenterology and gynecology, while those using Rosaceae for gastroenterology, urology, and neurology. For mixtures, Lamiaceae plants are also represented and used for gastroenterology, respiratory system treatment, and gynecology., Conclusion: The medicinal knowledge described in Sejfer derech ejc ha-chajim fills a gap in contemporary knowledge regarding phyto-medical writing of the Renaissance. The Guide has a form of home first aid kit, used both for medicinal purposes and on the daily menu. In response to current challenges in healthcare, there is a growing interest among researchers in ethnomedicinal sources for the discovery of novel therapeutic compounds. This includes the re-evaluation of formulations and therapeutic indications that have been recognised for centuries. The remedies analysed and detailed in The Guide can provide valuable insights for researchers focused on identifying biologically active therapeutic raw materials of plant origin, thus contributing to advances in modern healthcare., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Plant-derived exosome-like nanovesicles (PDNVs) are small nanoscale vesicles containing lipids, RNAs, proteins and some plant natural products secreted by plant cells. Over the last decade, PDNVs have garnered significant interest due to its exceptional therapeutic benefits in the treatment of various diseases. Herbal medicine, as a medicinal plant, plays an important role in the treatment of diseases including cancer. Especially in recent years, the function of herbal medicine derived exosome-like nanovesicles (HMDNVs) in the treatment of cancer has been widely concerned, and has become a research hotspot of nanomedicine. In this review, the biological characteristics, functions and the therapeutic advantages of PDNVs are reviewed, as well as the recent achievements and research progress of HMDNVs in cancer treatment, demonstrating its enormous promise as a cancer therapy, and new insights are provided for future research and development of anti-tumor drugs., Competing Interests: The authors report no conflicts of interest in this work., (© 2024 Chu et al.)

Background and Objectives : Heart failure with reduced ejection fraction (HFrEF) remains a significant burden. Traditional herbal medicines have shown cardioprotective effects in treating HFrEF. However, the implications of herbal formulation considering the dynamic immunohistological changes in the myocardium following acute ischemic injury have been insufficiently discussed. This review investigated the efficacy and mechanisms reported in studies using rat or mouse models of HFrEF induced by left descending coronary artery ligation. Materials and Methods : A systematic search was conducted using PubMed, Embase, AMED, CINAHL, and CENTRAL databases. Information was extracted regarding study characteristics, disease model induction protocols, intervention characteristics, treatment protocols, outcomes, and suggested mechanisms. Hierarchical cluster analysis of test drugs was performed based on constituent herb similarities. The risk of bias (RoB) was assessed using the Systematic Review Center for Laboratory animal Experimentation RoB tool. Results : Overall, 26 studies met the eligibility criteria. HF model induction periods after LADCA ligation ranged from 1 day to 12 weeks. Most studies administered the test drug for four weeks. Commonly used herbs included Panax ginseng , Astragalus membranaceus , Salvia miltiorrhiza , Carthamus tinctorius , and Lepidium apetalum , which demonstrated anti-fibrotic, anti-inflammatory, and anti-apoptotic effects through various signaling pathways. The overall RoB was relatively high. No significant association was found between model induction periods and herbal formulations or examined mechanisms. Conclusions : Future research should consider the time-dependent immunohistological features of the myocardium during HF treatment.

BACKGROUND The use of herbal medicines (HMs) is increasing, which raises concerns of herb-drug interactions (HDIs). This questionnaire-based study aimed to evaluate knowledge of HMs and HDIs in 147 undergraduate nursing students in Riyadh, Saudi Arabia, between March 2022 to June 2022. MATERIAL AND METHODS An online cross-sectional study was conducted among 147 nursing undergraduates at King Saud University, Riyadh, Saudi Arabia from March 2022 to June 2022, using a self-administered 24-item questionnaire. The convenience sampling method was used to evaluate the knowledge of HMs and interactions of anticoagulants, anti-inflammatory drugs, antibiotics, and antiplatelet drugs with herbs like ginkgo biloba, St. John's wort, garlic, ginger, green tea, and chamomile tea. RESULTS The findings of this study reported that 74.8% of the undergraduates used HMs. With regard to HDIs, 20.4% of nursing undergraduates identified the interaction between gingko biloba and drugs like ibuprofen and warfarin, while 13.6% identified interactions between drugs like warfarin with green tea, ginger, and chamomile tea. Regarding general knowledge, 59% of the students (n=84) reported good knowledge of HMs. Previous history of HM use significantly affected the mean HM knowledge score (t=4.635; P=0.0001). CONCLUSIONS To summarize, Saudi nursing students showed a lack of understanding and knowledge of HDIs. Ability to identify specific HDIs, like ginkgo biloba interactions with warfarin and ibuprofen, and warfarin interactions with green tea and ginger, was limited. There is a need to introduce HM and HDI courses in the academic curriculum.

Introduction: The prevalence of cardiac arrhythmia, which can lead to cardiac death, heart failure, and cardioembolic stroke, is increasing. Although various Western medicines for cardiac arrhythmias have been developed, there are still various difficulties in the management of arrhythmias. Traditional herbal medicines (THM) are widely used to manage arrhythmia in East Asia. Therefore, this study aimed to assess the effectiveness and safety of THM in the treatment of arrhythmia., Method: Using a systematic review methodology, we searched for randomized clinical trials on herbal medicines for arrhythmia without complications in 4 databases up to September 2022. The literature search was carried out again, targeting papers published until April 2024.We conducted a risk-of-bias assessment and meta-analysis. This study was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines., Results: Eighty-two randomized clinical trials were included in this meta-analysis. Total effective rate was significantly better in unspecified arrhythmia (risk ratio [RR]: 1.20, 95% confidence interval [CI]: 1.13-1.26), premature ventricular contraction (RR: 1.29, 95% CI: 1.29-1.33), sinus bradycardia (RR: 1.26, 95% CI: 1.17-1.36), tachycardia (RR: 1.23 95% CI: 1.15-1.32), and atrial fibrillation (RR: 1.17, 95% CI: 1.07-1.27). No severe adverse events were associated with THM. The overall risk of bias was relatively high. The total effective rate was the most frequently assessed clinical outcome variable. Most outcomes were surrogates and not clinical endpoints., Conclusion: THM, alone or in combination with Western medicine, has therapeutic effects on cardiac arrhythmic diseases. However, additional disease-specific clinical outcome variables are required for further studies on THM. Owing to the low quality of the included studies and their small sample sizes, additional large-scale, long-term follow-up, and well-designed randomized controlled clinical trials are required., Systematic Review Registration Number: Details of the protocol for this systematic review and meta-analysis were registered on the Open Science Framework (OSF. io). (https://osf.io/7r8kn/)., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Traditionally, herbal medicines have been used to alleviate nausea and vomiting; however, a comprehensive clinical evaluation for postoperative nausea and vomiting (PONV), especially after laparoscopic surgery, remains limited. This review aimed to evaluate the efficacy and safety of herbal medicine as an alternative therapy to prevent and manage nausea and vomiting after laparoscopic surgery compared with untreated, placebo, and Western medicine groups., Methods: We searched 11 databases, including EMBASE, PubMed, and the Cochrane Library, to collect randomized controlled trials (RCTs) of herbal medicines on PONV after laparoscopic surgery on July 7, 2022. Two independent reviewers screened and selected eligible studies, extracted clinical data, and evaluated the quality of evidence using the Cochrane risk-of-bias tool. The primary outcome was the incidence of PONV, whereas the secondary outcomes included the frequency and intensity of PONV, symptom improvement time, antiemetic requirement frequency, and incidence of adverse events. Review Manager Version 5.3. was used for the meta-analysis., Results: We identified 19 RCTs with 2726 participants comparing herbal medicine with no treatment, placebo, and Western medicine. The findings showed that compared with no treatment, herbal medicine demonstrated significant effects on vomiting incidence (risk ratio [RR] = 0.43, 95% confidence interval [CI] 0.32-0.57, P < .00001). Compared with placebo, herbal medicine revealed a significant effect on the severity of nausea 12 hours after laparoscopic surgery (standardized mean difference = -2.04, 95% CI -3.67 to -0.41, P = .01). Herbal medicines showed similar effects with Western medicine on the incidence of postoperative nausea (RR = 0.94, 95% CI 0.63-1.42, P = .77) and vomiting (RR = 0.68, 95% CI 0.25-1.84, P = .45). Furthermore, comparing the experimental group containing herbal medicine and control group excluding herbal medicine, adverse events were considerably lower in the group with herbal medicine (RR = 0.45, 95% CI 0.27-0.72, P = .001)., Conclusion: Herbal medicine is an effective and safe treatment for nausea and vomiting secondary to laparoscopic surgery. However, the number of studies was small and their quality was not high; thus, more well-designed RCTs are warranted in the future., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

The toll-like receptor 4 (TLR4) signaling pathway constitutes an intricate network of protein interactions primarily involved in inflammation and cancer. This pathway triggers intracellular signaling cascades, modulating transcription factors that regulate gene expression related to immunity and malignancy. Previous studies showed that colon cancer patients with low TLR4 expression exhibit extended survival times and the TLR4 signaling pathway holds a significant role in CRC pathogenesis. In recent years, traditional Chinese medicines (TCMs) have garnered substantial attention as an alternative therapeutic modality for CRC, primarily due to their multifaceted composition and ability to target multiple pathways. Emerging evidence indicates that specific TCM products, such as andrographolide, rosmarinic acid, baicalin, etc., have the potential to impede CRC development through the TLR4 signaling pathway. Here, we review the role and biochemical processes of the TLR4 signaling pathway in CRC, and natural products from TCMs affecting the TLR4 pathway. This review sheds light on potential treatment strategies utilizing natural TLR4 inhibitors for CRC, which contributes to the advancement of research and accelerates their clinical integration into CRC treatment.

Cynometra iripa Kostel. is a Fabaceae species of mangrove used in traditional Ayurvedic medicine for treating inflammatory conditions. The present study aims to establish monographic botanical and chemical quality criteria for C. iripa leaf and bark as herbal substances and to evaluate their in vitro antioxidant potential. Macroscopic and microscopic qualitative and quantitative analyses, chemical LC-UV/DAD-ESI/MS profiling, and the quantification of key chemical classes were performed. Antioxidant activity was evaluated by DPPH and FRAP assays. Macroscopically, the leaf is asymmetrical with an emarginated apex and cuneate base. Microscopically, it shows features such as two-layered adaxial palisade parenchyma, vascular bundles surrounded by 3-6 layers of sclerenchyma, prismatic calcium oxalate crystals (5.89 ± 1.32 μm) along the fibers, paracytic stomata only on the abaxial epidermis (stomatal index-20.15), and non-glandular trichomes only on petiolules. The microscopic features of the bark include a broad cortex with large lignified sclereids, prismatic calcium oxalate crystals (8.24 ± 1.57 μm), and secondary phloem with distinct 2-5 seriated medullary rays without crystals. Chemical profile analysis revealed that phenolic derivatives, mainly condensed tannins and flavonoids, are the main classes identified. A total of 22 marker compounds were tentatively identified in both plant parts. The major compounds identified in the leaf were quercetin-3- O -glucoside and taxifolin pentoside and in the bark were B-type dimeric proanthocyanidins and taxifolin 3- O -rhamnoside. The total phenolics content was higher in the leaf (1521 ± 4.71 mg GAE/g dry weight), while the total flavonoids and condensed tannins content were higher in the bark (82 ± 0.58 mg CE/g and 1021 ± 5.51 mg CCE/g dry weight, respectively). A total of 70% of the hydroethanolic extracts of leaf and bark showed higher antioxidant activity than the ascorbic acid and concentration-dependent scavenging activity in the DPPH assay (IC 50 23.95 ± 0.93 and 23.63 ± 1.37 µg/mL, respectively). A positive and statistically significant ( p < 0.05) correlation between the phenol content and antioxidant activity was found. The results obtained will provide important clues for the quality control criteria of C. iripa leaf and bark, as well as for the knowledge of their pharmacological potential as possible anti-inflammatory agents with antioxidant activity.

Rheumatoid arthritis (RA) stands as an autoimmune disorder characterized by chronic joint inflammation, resulting in profound physiological alterations within the body. Affecting approximately 0.4-1.3% of the global population, this condition poses significant challenges as current therapeutic approaches primarily offer symptomatic relief, with the prospect of complete recovery remaining elusive. This review delves into the contemporary advancements in understanding the pathophysiology, diagnosis, and the therapeutic potential of herbal medicine in managing RA. Notably, early diagnosis during the initial stages emerges as the pivotal determinant for successful recovery post-treatment. Utilizing tools such as Magnetic Resonance Imaging (MRI), anti-citrullinated peptide antibody markers, and radiography proves crucial in pinpointing the diagnosis of RA with precision. Unveiling the intricate pathophysiological mechanisms of RA has paved the way for innovative therapeutic interventions, incorporating plant extracts and isolated phytoconstituents. In the realm of pharmacological therapy for RA, specific disease-modifying antirheumatic drugs have showcased commendable efficacy. However, this conventional approach is not without its drawbacks, as it is often associated with various side effects. The integration of methodological strategies, encompassing both pharmacological and plant-based herbal therapies, presents a promising avenue for achieving substantive recovery. This integrated approach not only addresses the symptoms but also strives to tackle the underlying causes of RA, fostering a more comprehensive and sustainable path towards healing., (© 2024. The Author(s).)

Objective: To evaluate the efficacy and safety of herbal medicine and acupuncture combination for pediatric epilepsy treatment., Methods: Databases were searched from their interception until October 2023 to identify randomized controlled trials focusing on the therapeutic efficacy of herbal medicine-acupuncture combination (intervention group) for pediatric epilepsy. The primary outcome was the risk of treatment failure, whereas the secondary outcomes included the risk of post-treatment electroencephalogram (EEG) abnormalities and adverse events. Subgroup analyses were conducted based on the type of herbal compound formulas. Meta-regression analysis was conducted to examine the influence of patient demographics and clinical history on the therapeutic efficacy of herbal medicine-acupuncture combination for pediatric epilepsy. To assess the cumulative evidence, trial sequential analysis (TSA) was performed., Results: The analysis included 10 trials involving a total of 882 pediatric patients. Meta-analysis revealed that the intervention group had a lower risk of treatment failure than the control group (risk ratio [RR] = 0.3, 95% confidence interval [CI]: 0.19-0.47, P<0.00001, I2 = 0%, 10 trials). Subgroup analyses showed that therapeutic efficacy was consistent among the different herbal compound formulas. Meta-regression analysis revealed that the efficacy of the treatments did not significantly vary with patient age, male sex, and duration of seizure history. TSA suggested that herbal medicine-acupuncture combination exerted a robust and conclusive effect on seizure treatment. Although the combined used of herbal medicine and acupuncture was not associated with a lower risk of post-treatment EEG abnormalities (RR = 0.82, 95%CI:0.6-1.11, P = 0.2, 3 trials), the risk of adverse events was reduced (RR = 0.27, 95%CI:0.18-0.41, P<0.00001, 4 trials)., Conclusion: The meta-analysis suggested that combined use of herbal medicine and acupuncture is a promising and safe clinical approach for pediatric epilepsy treatment. Further large-scale studies are necessary to conclusively determine the efficacy and safety of herbal medicine and acupuncture in pediatric epilepsy treatment., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Su et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Shikimic acid (SA) is one of the most effective drugs against the A (H1N1) virus and has high medicinal value. Additionally, it has the ability to generate non-toxic herbicides and antimicrobial medications. The extraction from plants has proven to be the main route of production of SA with economic benefits and environmental efficiency. Therefore, it is necessary to perform purification of SA from these herbal medicines before quantifying it. In this study, researchers employed a boronate affinity-based controlled oriented surface imprinting technique to produce molecularly imprinted polymers (MIPs) as highly effective solid phase extraction (SPE) adsorbents for the isolation and purification of SA. 3-Fluoro-4-formylphenylboronic acid functionalized silica nanoparticles were used as supporting materials for immobilizing SA. Poly(2-anilinoethanol) with a higher hydrophilic domain can be used as an effective imprinting coating. The prepared SA-imprinted silica nanoparticles exhibited several significant results, such as good specificity, high binding capacity (39.06 ± 2.24 mg g -1 ), moderate binding constant (6.61 × 10 -4 M -1 ), fast kinetics (8 min) and low binding pH (pH 5.0) toward SA. The replication of SA-imprinted silica nanoparticles was deemed satisfactory. The SA-imprinted silica nanoparticles could be still reused after seven adsorption-desorption cycles, which indicated high chemical stability. In addition, the recoveries of the proposed method for SA at three spiked level analysis in star aniseed and meadow cranesbill were 96.2% to 109.0% and 91.6% to 103.5%, respectively. The SA-imprinted silica nanoparticles that have been prepared are capable of identifying the target SA in real herbal medicines. Our approach makes sample pre-preparation simple, fast, selective and efficient.

Background: SH003, a novel herbal medicine comprising Huang-Qi, Dang-Gui, and Gua-Lou-Gen, has historical roots in traditional medicine with reported anticancer properties. The need to explore safe and effective treatments in oncology underlines the importance of this study., Methods: This phase I trial, conducted at Ajou University Hospital and Gachon University Gil Medical Center in Korea, adopted a single-arm, open-label, dose-escalation design. It aimed to evaluate the safety of escalated doses of SH003 in patients with various solid cancers, focusing on determining its maximum tolerated dose. Participants with confirmed solid cancers, unresponsive to standard treatments, were enrolled. The dosage of SH003 was escalated from 4800 to 9600 mg per day, using a 3 + 3 design. Safety was assessed based on the Common Terminology Criteria for Adverse Events ver. 5.0., Results: The study established that the maximum tolerated dose of SH003 is 9600 mg/day. Most adverse events were mild, primarily including dizziness and nausea, indicating the tolerability of SH003 at this dosage., Conclusions: SH003 demonstrates safety and promises as an anticancer treatment at doses up to 9600 mg/day. This research supports further investigation into its efficacy for cancer therapy, emphasizing the significance of natural products in oncology, particularly concerning patient safety and tolerance., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Aims: This study aimed to assess the habits and knowledge of cancer patients regarding the use of herbal medicines and dietary supplements in cancer patients receiving immune checkpoint inhibitors (ICI)., Methods: The data of 181 cancer patients who were over 18 years old and received ICIs were collected. The usage patterns, anticipated benefits and harms, and sources of supply were evaluated by filling researcher-prepared forms., Results: Most patients did not use any kind of herbal medicine (91.2%) or dietary supplements (75.9%) during their immunotherapy. Boosting the immune system is the primary motivation for use among users. Multivitamins are the most frequently used supplements. Family members and TV advertisements were the main sources of information, in addition to limited advice from healthcare professionals. A minority of participants reported gastrointestinal side effects. Herbal medicine and dietary supplement use were more prevalent among patients with stage IV cancer and renal cell carcinoma (RCC)., Discussion: This study revealed that the limited uptake of herbal medicines and dietary supplements alongside ICI treatment among cancer patients. The lack of adequate information from healthcare professionals poses potential risks to patients. Improved communication with patients, education regarding herbal medicine and dietary supplement use, potential interactions, and associated risks during ICI treatment are essential. Further research is needed to identify the specific needs of patients, anticipated benefits, and potential harms of herbal medicine and dietary supplement use, together with ICIs., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Preserving host health and homeostasis is largely dependent on the human gut microbiome, a varied and ever-changing population of bacteria living in the gastrointestinal tract. This article aims to explore the multifaceted functions of the gut microbiome and shed light on the evolving field of research investigating the impact of herbal medicines on both the composition and functionality of the gut microbiome. Through a comprehensive overview, we aim to provide insights into the intricate relationship between herbal remedies and the gut microbiome, fostering a better understanding of their potential implications for human health.The gut microbiota is composed of trillions of microorganisms, predominantly bacteria, but also viruses, fungi, and archaea. It functions as a complex ecosystem that interacts with the host in various ways. It aids in nutrient metabolism, modulates the immune system, provides protection against pathogens, and influences host physiology. Moreover, it has been linked to a range of health outcomes, including digestion, metabolic health, and even mental well-being. Recent research has shed light on the potential of herbal medicines to modulate the gut microbiome. Herbal medicines, derived from plants and often used in traditional medicine systems, contain a diverse array of phytochemicals, which can directly or indirectly impact gut microbial composition. These phytochemicals can either act as prebiotics, promoting the growth of beneficial bacteria, or possess antimicrobial properties, targeting harmful pathogens. Several studies have demonstrated the effects of specific herbal medicines on the gut microbiome. For example, extracts from herbs have been shown to enhance the abundance of beneficial bacteria, such as Bifidobacterium and Lactobacillus, while reducing potentially harmful microbes. Moreover, herbal medicines have exhibited promising antimicrobial effects against certain pathogenic bacteria. The modulation of the gut microbiome by herbal medicines has potential therapeutic implications. Research suggests herbal interventions could be harnessed to alleviate gastrointestinal disorders, support immune function, and even impact metabolic health. However, it is important to note that individual responses to herbal treatments can vary due to genetics, diet, and baseline microbiome composition. In conclusion, the gut microbiome is a critical player in maintaining human health, and its modulation by herbal medicines is a burgeoning area of research. Understanding the complex interactions between herbal compounds and gut microbiota will pave the way for innovative approaches to personalized healthcare and the development of herbal-based therapeutics aimed at promoting gut health and overall well-being., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Background: Natural products are increasingly gaining interest as potential new drug candidates for cancer treatment. Herbal formula, which are combinations of several herbs, are primarily used in East Asia and have a long history of use that continues today. Recently, research exploring the combination of herbal formulas and chemotherapy for cancer treatment has been on the rise., Methods: This study reviewed research on the co-administration of herbal formulas and chemotherapy for cancer treatment. The databases PubMed, Embase, and Cochrane Library were used for article searches. The following keywords were employed: "Antineoplastic agents," "Chemotherapy," "Phytotherapy," "Herbal medicine," "Drug synergism," and "Synergistic effect." The selection process focused on studies that investigated the synergistic interaction between herbal formulas and chemotherapeutic agents., Results: Among the 30 studies included, 25 herbal formulas and 7 chemotherapies were used. The chemotherapy agents co-administered included cisplatin, 5-fluorouracil, docetaxel, doxorubicin, oxaliplatin, irinotecan, and gemcitabine. The types of cancer most frequently studied were lung, breast, and colon cancers. Most studies evaluating the anticancer efficacy of combined herbal formula and chemotherapy treatment were conducted in vitro or in vivo., Discussion: Most studies reported synergistic effects on cytotoxicity, apoptosis, and tumor growth inhibition. These effects were found to be associated with cell cycle arrest, anti-angiogenesis, and gene expression regulation. Further studies leading to clinical trials are required. Clinical experiences in East Asian countries could provide insights for future research., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: The use of herbal medicine (HM) as a self-management practice for treating various diseases has gained popularity worldwide. Consumers co-administer herbal products with conventional medicine without the knowledge of possible herb-drug interaction (HDI)., Aim: This study aimed to assess patients' perception and use of HM and their knowledge of HDI., Setting: Participants attending primary health care (PHC) clinics in three provinces (Gauteng, Mpumalanga and Free State), South Africa, were recruited., Methods: Focus group discussions comprising a total of thirty (N = 30) participants were conducted using a semi-structured interview guide. Discussions were audio-recorded and then transcribed verbatim. Data were analysed using thematic content analysis., Results: Reasons for using HM, sources of information on HM, co-administration of HM and prescribed medicine, disclosure of the use of HM, PHC nurses' attitudes and not having time to engage were frequently discussed. Respondents' lack of knowledge and perceptions about HDI and their dissatisfaction with prescribed medicine because of experienced side effects were also discussed., Conclusion: Because of the lack of discussions and non-disclosure about HM in PHC clinics, patients are at risk of experiencing HDIs. Primary health care providers should regularly enquire about HM use on every patient, to identify and prevent HDIs. The lack of knowledge about HDIs by patients further compromises the safety of HM.Contribution: The results highlighted the lack of knowledge of HDI by patients thus assisting the healthcare stakeholders in South Africa to implement measures to educate patients attending PHC clinics.

Background: Clinical research in natural product-based psychopharmacology has revealed a variety of promising herbal medicines that may provide benefit in the treatment of mild mood disorders, however failed to unambiguously indicate pharmacologically active constituents. The emerging role of the microbiota-gut-brain axis opens new possibilities in the search for effective methods of treatment and prevention of mood disorders., Purpose: Considering the clinically proven effectiveness juxtaposed with inconsistencies regarding the indication of active principles for many medicinal plants applied in the treatment of anxiety and depression, the aim of the review is to look at their therapeutic properties from the perspective of the microbiota-gut-brain axis., Method: A literature-based survey was performed using Scopus, Pubmed, and Google Scholar databases. The current state of knowledge regarding Hypericum perforatum, Valeriana officinalis, Piper methysticum, Passiflora incarnata, Humulus lupulus, Melissa officinalis, Lavandula officinalis, and Rhodiola rosea in terms of their antimicrobial activity, bioavailability, clinical effectiveness in depression/anxiety and gut microbiota - natural products interaction was summarized and analyzed., Results: Recent studies have provided direct and indirect evidence that herbal extracts and isolated compounds are potent modulators of gut microbiota structure. Additionally, some of the formed postbiotic metabolites exert positive effects and ameliorate depression-related behaviors in animal models of mood disorders. The review underlines the gap in research on natural products - gut microbiota interaction in the context of mood disorders., Conclusion: Modification of microbiota-gut-brain axis by natural products is a plausible explanation of their therapeutic properties. Future studies evaluating the effectiveness of herbal medicine and isolated compounds in treating mild mood disorders should consider the bidirectional interplay between phytoconstituents and the gut microbiota community., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Background: To investigate the efficacy of Qingre Lishi Decoction(QLRD), in the treatment of acute gouty arthritis, and its influence on the expression levels of inflammatory factor nucleotide-binding oligomerization domain-like receptor(NALP 3) in patients., Methods: A total of 78 patients with acute gouty arthritis admitted to our hospital were randomly divided into the control group and the observation group, with 39 cases in each group. The control group was given basic treatment and colchicine tablets, and the observation group was given "heat-clearing and diuresis-promoting" prescription for intervention treatment. The main symptom score, treatment effective rate and laboratory indexes of the two groups were compared 7 days after treatment., Results: After treatment, the scores of joint redness, hot pain, joint flexion and extension disorder, oliguria and constipation were improved in both groups, and the improvement degree in observation group was higher than that in control group (P < 0.05); the clinical effective rate in the observation group (94.87%) was higher than that in the control group (76.92%). The serum uric acid (UA), erythrocyte sedimentation rate (ESR), interleukin-1β (IL-1β) and NALP3 showed a decreasing trend, and the decrease degree of each index in observation group was higher than that in control group (P < 0.05)., Conclusion: The "heat-clearing and diuresis-promoting" prescription for intervention treatment can effectively improve the clinical symptoms of patients with acute gouty arthritis and reduce the level of inflammatory factor NALP3, maintaining remarkable effect., (© 2022. The Author(s).)

The pandemic of coronavirus disease 2019 (COVID-19) caused by the SARS-coronavirus 2(SARS-CoV-2) virus has become the greatest global public health crisis in recent years,and the COVID-19 epidemic is still continuing. However, due to the lack of effectivetherapeutic drugs, the treatment of corona viruses is facing huge challenges. In thiscontext, countries with a tradition of using herbal medicine such as China have beenwidely using herbal medicine for prevention and nonspecific treatment of corona virusesand achieved good responses. In this review, we will introduce the application of herbalmedicine in the treatment of corona virus patients in China and other countries, andreview the progress of related molecular mechanisms and antiviral activity ingredients ofherbal medicine, in order to provide a reference for herbal medicine in the treatment ofcorona viruses. We found that herbal medicines are used in the prevention and fightagainst COVID-19 in countries on all continents. In China, herbal medicine has beenreported to relieve some of the clinical symptoms of mild patients and shorten the length of hospital stay. However, as most herbal medicines for the clinical treatment of COVID-19still lack rigorous clinical trials, the clinical and economic value of herbal medicines in theprevention and treatment of COVID-19 has not been fully evaluated. Future work basedon large-scale randomized, double-blind clinical trials to evaluate herbal medicines andtheir active ingredients in the treatment of new COVID-19 will be very meaningful.

Post-stroke insomnia (PSI) is a highly prevalent complication after stroke. Current evidence of psychotropic drug use for PSI management is scarce and indicates harmful adverse events (AEs). Traditional East Asian herbal medicine is a widely used traditional remedy for insomnia. However, so far, no study has systematically reviewed the efficacy and safety of traditional east asian herbal medicine (HM) for PSI. Therefore, we perform meta-analysis to evaluate the effectiveness and safety of HM for PSI. After a comprehensive electronic search of 15 databases, we review the randomized controlled trials (RCTs) of HM use as monotherapy for PSI. Our outcomes were the Pittsburgh sleep quality index and total effective rate. In total, 24 RCTs were conducted with 1942 participants. HM showed statistically significant benefits in sleep quality. It also appeared to be safer than psychotropic drugs in terms of AEs, except when the treatment period was two weeks. The methods used for RCTs were poor, and the quality of evidence assessed was graded "low" or "moderate." The findings of this review indicate that the use of HM as a monotherapy may have potential benefits in PSI treatment when administered as an alternative to conventional medications. However, considering the methodological quality of the included RCTs, we were uncertain of the clinical evidence. Further, well-designed RCTs are required to confirm these findings.

Autoimmune thyroiditis (AIT), one of the most common autoimmune diseases among women of reproductive age, is closely associated with reproductive failure and other obstetric complications. However, effective clinical strategies for the management of pregnant women with AIT are limited. It has been shown that Prunella vulgaris (PV), a traditional herbal medicine, can ameliorate AIT and other common thyroid disorders. Therefore, using an experimental autoimmune thyroiditis (EAT) rat model, we investigated the potential effects of PV on AIT-related pregnancy outcomes. According to the administered dose of PV, EAT rats were randomly divided into the untreated EAT and PV-treated EAT groups. We found that thyroid peroxidase antibody and thyroglobulin antibody serum levels and the inflammatory infiltration of the thyroid were reduced in all PV-treated groups. Increased splenic Tgfb1 mRNA levels and Treg cell proportions were associated with decreased Th1/Th17 cell proportions, and Ifng mRNA levels were reduced in rats that received low and medium doses of PV. Moreover, in the low-dose PV group, fetal development retardation and placental injuries were reversed. Overall, our findings indicated that PV could alleviate AIT and improve pregnancy outcomes in EAT rats by downregulating Th1/Th17 immune responses and inducing Treg cell proliferation., (Copyright © 2021. Published by Elsevier B.V.)

In the present study, thirty two lactic acid bacteria (LAB) were isolated from fermented Indian herbal medicine. In comparison to other strains, MNL5 had stronger bile salt hydrolase (BSH) and cholesterol-lowering properties. Furthermore, it can withstand the extreme conditions found in the GI tract, due to, e.g., pepsin, bile salts, pancreatin, and acids. Pediococcus acidilactici MNL5 was identified as a probiotic candidate after sequencing the 16S rRNA gene. The antibacterial activity of P. acidilactici MNL5 cell-free supernatants (CFS) against Escherichia coli , Staphylococcus aureus , Helicobacter pylori, Bacillus cereus , and Candida albicans was moderate. A Caenorhabditis elegans experiment was also performed to assess the effectiveness of P. acidilactici MNL5 supplementation to increase life span compared to E. coli supplementation (DAF-2 and LIU1 models) ( p < 0.05). An immense reduction of the lipid droplets of C. elegans was identified through a fluorescent microscope. The drastic alteration of the expression of fat genes is related to obesity phenotypes. Hence, several paths are evolutionary for C. elegans ; the results of our work highlight the nematode as an important model for obesity.

Parkin is a crucial E3 ubiquitin ligase for initiating mitophagy through the PINK1/Parkin pathway. Regulating the expression and activity of parkin can remedy mitophagy and human disease. We developed an efficient method to isolate natural parkin ligands from herbal medicines by combining centrifugal ultrafiltration and liquid chromatography/mass spectrometry. The heterologous expression technology identified functionally active and pure parkin proteins. After evaluating the reliability of the method using DL-selenomethionine and DL-dithiothreitol as positive controls, this method was successfully applied to capture parkin ligands from Polygoni Cuspidati Rhizoma et Radix and Sophorae Flavescentis Radix. LC/MS identified seven novel parkin-targeting compounds, namely, 7,4'-dihydroxy-5-methoxy-8-( γ , γ -dimethylallyl)-flavanone, kushenol I, kurarinone, sophoraflavanone G, torachrysone-8-O-glucoside, apigenin, and emodin, supported by the molecular docking analysis. Five of the seven novel compounds (kushenol I, kurarinone, sophoraflavanone G, apigenin, and emodin) can activate parkin in in vitro autoubiquitination assays. Meanwhile, kushenol I and kurarinone had antisteatosis activity in fat emulsion-damaged human hepatocytes. These results confirmed the effectiveness of the method for identifying parkin ligands from complex preparations, useful to advance drug discovery from medicinal herbs., Competing Interests: The authors declare no conflicts of interest associated with this manuscript., (Copyright © 2022 Feng-Jiao Li et al.)

Lasia spinosa (L.) is used ethnobotanically for the treatment of various diseases, including rheumatoid arthritis, inflammation of the lungs, bleeding cough, hemorrhoids, intestinal diseases, stomach pain, and uterine cancer. This review is aimed at summarizing phytochemistry and pharmacological data with their molecular mechanisms of action. A search was performed in databases such as PubMed, Science Direct, and Google Scholar using the keywords: " Lasia spinosa ," then combined with "ethnopharmacological use," "phytochemistry," and "pharmacological activity." This updated review included studies with in vitro, ex vivo, and in vivo experiments with compounds of known concentration and highlighted pharmacological mechanisms. The research results showed that L. spinosa contains many important nutritional and phytochemical components such as alkanes, aldehydes, alkaloids, carotenoids, flavonoids, fatty acids, ketones, lignans, phenolics, terpenoids, steroids, and volatile oil with excellent bioactivity. The importance of this review lies in the fact that scientific pharmacological evidence supports the fact that the plant has antioxidant, anti-inflammatory, antimicrobial, cytotoxic, antidiarrheal, antihelminthic, antidiabetic, antihyperlipidemic, and antinociceptive effects, while protecting the gastrointestinal system and reproductive. Regarding future toxicological and safety data, more research is needed, including studies on human subjects. In light of these data, L. spinosa can be considered a medicinal plant with effective bioactives for the adjuvant treatment of various diseases in humans., Competing Interests: The authors declare that they have no competing interests., (Copyright © 2021 Rajib Hossain et al.)

Background: Functional dyspepsia (FD) has gradually developed into a multiple disease of the digestive system that most patients may be accompanied by mental and emotional disorders, such as insomnia, anxiety, and depression. Acupoint herbal patching (AHP) is usually used as an alternative therapy for patients with FD. This study aimed to design a systematic review and meta-analysis to explore the effects of AHP on FD., Methods: We will search the Cochrane Central Register of Controlled Trials, the Web of Science, PubMed, Embase, the Chinese Biomedical Literature Database, the Chinese Scientific Journal Database, the Wan-Fang Database, and the China National Knowledge Infrastructure for randomized controlled trials of FD treated by AHP from inception to June 30, 2021. The primary outcome measures contain clinical effective rate, the symptom score of FD, and secondary outcome measures consist of quality of life, incidence of adverse events, and recurrence rate. We will use RevMan V.5.3 software to analyze data. Two reviewers will evaluate the risk of bias and the quality of the studies by the Cochrane Collaboration risk of bias tool and the Grading of Recommendations Assessment, Development, and Evaluation approach, separately., Results: This systematic review protocol will analyze the effectiveness, quality of life, improvement of the symptom, and safety of AHP therapy for FD., Conclusion: The findings of this systematic review will provide evidence to evaluate the effectiveness and safety of AHP for FD., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Glucocorticoids are drugs that are widely used to suppress inflammation and the activation of the immune system. However, the prolonged use or at high doses of glucocorticoid can result in adverse side effects including osteoporosis, bone loss, and an increased risk of fracture. A number of compounds derived from natural plant sources have been reported to exert anti-inflammatory activity by interacting with the glucocorticoid receptor (GR), likely owing to their chemical similarity to glucocorticoids, or by regulating GR, without a concomitant risk of treatment-related side effects such as osteoporosis. Other herbal compounds can counteract the pathogenic processes underlying glucocorticoid-induced osteoporosis (GIOP) by regulating homeostatic bone metabolic processes. Herein, we systematically searched the PubMed, Embase, and Cochrane library databases to identify articles discussing such compounds published as of May 01, 2021. Compounds reported to exert anti-inflammatory glucocorticoid-like activity without inducing GIOP include escin, ginsenosides, and glycyrrhizic acid, while compounds reported to alleviate GIOP by improving osteoblast function or modulating steroid hormone synthesis include tanshinol and icariin., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhang, Li, Ying, Wang and Fu.)

Background: Henoch-Schönlein purpura nephritis (HSPN) is listed as the most common secondary glomerular diseases among children. Approximately 15 to 20% of children eventually could develop into chronic renal failure. Chinese patent herbal medicine Huaiqihuang (HQH) has been widely used in children with HSPN. This study aimed to evaluate the effectiveness and safety of HQH for HSPN in children, so as to provide evidence for clinical use., Methods: Randomized controlled trials (RCTs) on HQH for HSPN in children were searched in eight Chinese and English databases from their inception to December 2020. We included children with HSPN received HQH combined with conventional medicine. Cochrane "Risk of bias" tool was used to assess methodological quality, and "Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach" to summarize the certainty of evidence for main findings. Effect estimates were presented as risk ratio (RR), mean difference (MD) or standardized mean difference (SMD) with 95% confidence interval (CI) in meta-analyses using RevMan 5.3. Data not suitable for statistical pooling were synthesized qualitatively., Results: In total seven RCTs were identified. Compared with conventional medicine alone, HQH plus conventional medicine showed the better effect in improving clinical cure rate (RR 1.58; 95%CI 1.17 to 2.14; n = 6) and total effective rate (RR 1.34; 1.16 to 1.54; n = 6); reducing urine sediment erythrocyte count (MD -9.23; - 10.76 to - 7.69; n = 3) and urine β2 micro-globulin level (MD -0.09; - 0.12 to - 0.06; n = 2). No serious adverse event was recorded in all included trials., Conclusions: Limited evidence showed HQH combined with conventional medicine had a beneficial effect for children with HSPN, and the side effects were mild. HQH may be a promising complementary therapy. However, long term follow-up, high quality and multicenter RCTs are required to confirm the findings., (© 2021. The Author(s).)

The Taiwan Adverse Drug Reaction Reporting System for Herbal Medicine (TADRRS-HM) has systematically documented suspected adverse events from adverse drug reaction (ADR) reports from 1998 (prior to its formal establishment in 2001) and evaluates safety profiles of herbal medicines. This article describes findings from 2079 ADR reports filed between 1998 and 2016: 941 reports involved single herbs and 87 involved folk herbals; 842 were generated from clinical trials, while 209 ADR reports involving foods, health foods, dietary supplement foods and herbal cuisine were grouped as Other. Severity assessments using the Modified Hartwig and Siegel scale classified 72.4% of ADRs as mild, 17.4% as moderate and 6.5% as severe. System Organ Class classification of the ADRs identified gastrointestinal system disorders as the most common (33.4%), followed by skin and subcutaneous tissue disorders (21.2%). The TADRRS-HM records indicate that herbal medicines may cause a wide range of ADRs. Aconiti Radix, Xiao-Qing-Long-Tang, and Datura suaveolens were the most commonly reported single herb, herbal formula, and folk herbal, respectively. The data indicate that herbal medicines may cause a wide range of ADRs. This system will confer long-term benefits for the development of Taiwan's herbal medicines adverse reaction database and facilitate epidemiological analysis., (© 2021. The Author(s).)

Parkinson's disease (PD) is a complex neurodegenerative disease, manifested by the progressive functional impairment of the midbrain nigral dopaminergic neurons. Due to the unclear underlying pathogenesis, disease-modifying drugs for PD remain elusive. In Asia, such as in China and India, herbal medicines have been used in the treatment of neurodegenerative disease for thousands of years, which recently attracted considerable attention because of the development of curative drugs for PD. In this review, we first summarized the pathogenic factors of PD including protein aggregation, mitochondrial dysfunction, ion accumulation, neuroinflammation, and oxidative stress, and the related recent advances. Secondly, we summarized 32 Chinese herbal medicines (belonging to 24 genera, such as Acanthopanax , Alpinia , and Astragalus ), 22 Chinese traditional herbal formulations, and 3 Indian herbal medicines, of which the ethanol/water extraction or main bioactive compounds have been extensively investigated on PD models both in vitro and in vivo . We elaborately provided pictures of the representative herbs and the structural formula of the bioactive components (such as leutheroside B and astragaloside IV) of the herbal medicines. Also, we specified the potential targets of the bioactive compounds or extractions of herbs in view of the signaling pathways such as PI3K, NF- κ B, and AMPK which are implicated in oxidative and inflammatory stress in neurons. We consider that this knowledge of herbal medicines or their bioactive components can be favorable for the development of disease-modifying drugs for PD., Competing Interests: The authors declare no competing interests, (Copyright © 2021 Rong Yin et al.)

We conducted a prospective randomized study to investigate the effect of daikenchuto (DKT) on abdominal symptoms following laparoscopic colectomy in patients with left-sided colon cancer. Patients who suffered from abdominal pain or distention on postoperative day 1 were randomized to either the DKT group or non-DKT group. The primary endpoints were the evaluation of abdominal pain, abdominal distention, and quality of life. The metabolome and gut microbiome analyses were conducted as secondary endpoints. A total of 17 patients were enrolled: 8 patients in the DKT group and 9 patients in the non-DKT group. There were no significant differences in the primary endpoints and postoperative adverse events between the two groups. The metabolome and gut microbiome analyses showed that the levels of plasma lipid mediators associated with the arachidonic acid cascade were lower in the DKT group than in the non-DKT group, and that the relative abundance of genera Serratia and Bilophila were lower in the DKT group than in the non-DKT group. DKT administration did not improve the abdominal symptoms following laparoscopic colectomy. The effects of DKT on metabolites and gut microbiome have to be further investigated., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

The prevalence of Type 2 diabetes increases under conditions of obesity but also due to aging. While a variety of treatment options are being explored there are still many unanswered questions about the underlying mechanisms for the aetiology and progression of this illness. Here we show that pre-treatment with Ninjin'yoeito (NYT), a herbal medicine composed of 12 different ingrediencies, before a glucose challenge results in significantly improved glucose tolerance. This occurs in the absence of significant alterations in insulin excursion compared to vehicle treatment, indicating NYT improves insulin responsiveness and/or insulin-independent glucose disposal. Furthermore, we identify Ginseng - one of the 12 ingredients of NYT - as one key component contributing to NYT's effect on glucose clearance. Importantly, lack of Y4 receptor signalling abolishes the positive effects of NYT on glucose tolerance suggesting Y4 receptor-controlled pathways are crucial in mediating this action of NYT. Using c-fos as neuronal activation marker, we show NYT activates the area postrema - a circumventricular organ in the brainstem that expresses high level of Y4 receptors, supporting an involvement of brainstem Y4 signalling in NYT-activated central networks. Together, these data suggest that NYT is a positive influencer of glucose metabolism in insulin-sensitive tissues and the mechanistic actions of NYT include brainstem Y4 circuitries., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The world is currently struggling with the Coronavirus disease 2019 (COVID-19) pandemic. Dietary supplements (DSs) and herbal medicine provide a potentially convenient and accessible method for its recovery, but direct evidence is limited., Objective: This study aims to investigate the effectiveness of DSs and herbs in patients with COVID-19., Methods: A systematic literature search was conducted in multiple electronic English and Chinese databases. Randomized controlled trials (RCTs) involving DSs or herbal medicine interventions on patients with COVID-19 from November 2019 to February 2021 were included. Data was extracted, summarized and critically examined., Results: Out of 9402 records identified in the initial search, twelve RCTs were included in this review. Risk of bias of these RCTs was deemed high. Most of the trials were of low methodologic quality. Nine studies showed herbal supplements were beneficial to the recovery of COVID-19 patients; zinc sulfate could shorten the duration of loss of smell but not total recovery from COVID-19. No severe adverse events were reported., Conclusion: Herbal supplements may help patients with COVID-19, zinc sulfate is likely to shorten the duration of olfactory dysfunction. DS therapy and herbal medicine appear to be safe and effective adjuvant therapies for patients with COVID-19. These results must be interpreted with caution due to the overall low quality of the included trials. More well-designed RCTs are needed in the future., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2021 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

Background: Post-stroke insomnia (PSI) is a highly prevalent complication in patients with stroke. However, there has been no comprehensive systematic review assessing the efficacy and safety of herbal medicine (HM) on PSI. This protocol was developed to conduct a systematic review and meta-analysis to evaluate the evidence related to the efficacy and safety of HM on PSI., Methods: We will perform a comprehensive electronic search, including Medline, EMBASE, CENTRAL, AMED, CINAHL, PsycARTICLES, and Chinese, Korean, and Japanese databases from their inception to November 2020. This systemic review will include only randomized controlled clinical trials of HM on PSI. The main outcome is the Pittsburgh Sleep Quality Index score. Two researchers will independently screen citations and abstracts, identify full-text articles for inclusion, extract data, and appraise the quality and risk of bias of included studies. A meta-analysis will be conducted using Review Manager 5.4. The evidence quality of each outcome will be appraised according to Grades of Recommendation, Assessment, Development, and Evaluation., Results: This protocol adheres to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-P (PRISMA-P) guidelines to ensure clarity and completeness of reporting in all phases of the systematic review., Conclusion: This study will provide evidence regarding the efficacy and safety of HM for the treatment of PSI., Ethics and Dissemination: No ethical approval will be needed because data from previously published studies in which informed consent was obtained by primary investigators will be retrieved and analyzed. We will publish this systematic review in a peer-reviewed journal., Osf Registration Doi: 10.17605/OSF.IO/PEHQZ., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

In developing countries, populations have employed herbal medicines for primary health care because they are believed to be more appropriate to the human body and have less side effects than chemically synthesized drugs. The present study aimed to develop and evaluate herbal tablets incorporated with a Thai traditional medicinal extract, U-pa-ri-waat (URW), using microwave-assisted extraction (MAE). The extraction efficiency for URW using MAE and traditional solvent extraction was compared based on the percent yield after spray drying. URW tablets were prepared using the dry granulation method. The optimized products were assessed using standard characterization methods based on the United States and British Pharmacopeias. DPPH and ABTS radical scavenging assays were performed to analyze the antioxidant capacity of the microwave-assisted extracts. The results revealed that the flowability of the dry granule with added maltodextrin was improved compared to a granule without additives, as indicated by an angle of repose of 33.69 ± 2.0°, a compressibility index of 15.38 ± 0.66, and a Hausner's ratio of 1.18 ± 0.06. The resulting formulation produced flat tablets with uniform weight variation, hardness, thickness, friability, and optimum disintegration time. The URW extracts showed antioxidant activity and MAE with maltodextrin carrier displayed the strongest DPPH and ABTS radical activities with IC50 values of 1.60 ± 0.02 μg/mL and 4.02 ± 0.24 μg/mL, respectively. The URW tablet formulation passed the quality control tests. Storage of the formulation tablets for 90 days under accelerated conditions had minimal effects on tablet characteristics.

WangShiBoChiWan (WSBCW) is a commonly used Chinese herbal medicine for the treatment of functional gastrointestinal disorders. However, its preclinical efficacy and the mechanisms of action have not been adequately studied. The goals of this study were to evaluate the effects of WSBCW on gastrointestinal health and modulation of related biomarkers. Female C57BL mice were randomly assigned into one of the experimental groups consisting of the control, drug controls, and WSBCW at 40, 120, and 360 mg/kg BW. Whole gut transit, small intestinal motility, and intestinal barrier permeability were determined. The castor oil-induced diarrhea mouse model was used to determine the effect of WSBCW on the diarrhea type of irritable bowel syndrome (IBS-D). WSBCW increased whole gut transit and intestinal motility, improved intestinal permeability in healthy animals and alleviated diarrhea symptoms in IBS-D mice. WSBCW upregulated intestinal junction proteins, increased the abundance of Bifidobacterium genus, Desulfovibrio genus and inhibited Bacteroides fragillis group in the gut microbiota, increased intestinal villi lengths, and decreased blood levels of inflammatory cytokines. Our study provided preclinical evidence to verify the effectiveness of WSBCW in gastrointestinal health and elucidate mechanistic insights. The results warrant further investigations to evaluate the therapeutic efficacy of WSBCW on gastrointestinal disorders, such as IBS and IBD., (Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

Background: Idiopathic membranous nephropathy (IMN) is one of the most common causes of nephrotic syndrome in adults involving multiple targets and factors. The effect of conservative nonimmunosuppressive or immunosuppressive therapies is unsatisfactory and with many side effects. Traditional Chinese medicine (TCM) can regulate immune function and improve kidney function., Purpose: To evaluate the total effective rate, curative rate, recurrence rate and adverse events of TCM alone or TCM as an adjunctive therapy for IMN., Methods: Randomized controlled trials (RCT) comparing either TCM alone or the combination of TCM to western medicine (WM) therapies for patients with IMN were retrieved by searching English and Chinese database. Risk of bias summary was used to assess the methodological quality of eligible studies. Dichotomous data were presented using odds ratios (OR). The primary outcome measure was the total effective rate. Secondary outcomes included curative rate, recurrence rate and adverse events., Results: 29 RCTs involving 1883 participants met the inclusion criteria. There was no statistically significant difference between the therapy of TCM alone and WM on the total effective rates (OR: 2.00; 95% CI: 0.80-4.98; P = 0.14) and curative rate (OR: 1.66; 95%CI: 0.66-4.22; p = 0.28). However, compared to basic treatment or immunosuppressive therapies alone, results showed that TCM as an adjunctive therapy had beneficial effects on the total effective rate (OR: 2.59; 95% CI: 1.38-4.86; P = 0.003 and OR: 3.01; 95% CI: 2.25-4.04; P < 0.00001) and curative rate (OR: 3.01; 95%CI: 1.24-7.28; p = 0.01 and OR: 1.73; 95%CI: 1.10-2.71; p = 0.02). In addition, the combination of TCM treatment could reduce the recurrence rate (OR: 0.28; 95% CI: 0.12-0.68; P = 0.004) and adverse reactions (OR: 0.38; 95% CI: 0.27-0.54; p < 0.00001)., Conclusion: The results indicate that TCM is well-tolerated for the treatment of IMN. However, there remains a need for large-scale and high-quality trials., Competing Interests: The authors have declared that no competing interests exist.

Owing to modern developments in the traditional medicine industry, more people now acknowledge the efficacy of traditional medicine. As the demand for herbal medicines gradually increases, the focus of the industry will shift to how to increase production while maintaining the high quality of raw materials and final products to promote the international trade in herbal medicines. In the long history of herbal medicine, many countries and regions have formulated relevant standards to regulate the cultivation of local herbs to ensure the safety and reliability of the products. Due to cultural and historical differences, the policies for formulating herbal cultivation standards vary greatly between regions, which hinders the international trade of herbal medicines. This paper collates the guidelines of good agricultural and collection practices of the European Union, China, World Health Organization and the United States, and makes a comprehensive comparison of its contents such as production environments, production area suitability, air, soil, and water standard regulations, inter alia. This article aims to explore the differences in good agriculture and collection practice in herbal medicine in various regions and provides a reference for the development of international guidelines for herbal quality management, which will aid with the development of herbal medicine quality standardization globally and exchange services in the trade of herbal medicines., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Post-stroke constipation is a major complication of stroke and increases the incidence of poor neurological outcomes and infectious complications and, therefore, warrants active and prompt treatment. In East Asian countries, several types of herbal medicines have been used for the treatment of post-stroke constipation because they are considered safer than existing pharmacotherapies. However, no systematic review has investigated the efficacy and safety of traditional East Asian herbal medicine in the treatment of post-stroke constipation. With this systematic review and meta-analysis, we aimed to evaluate the efficacy and safety of traditional East Asian herbal medicines for the treatment of post-stroke constipation., Methods and Analysis: Eight electronic databases will be searched for relevant studies published from inception to April 2021. Only randomized controlled trials (RCTs) that assess the efficacy and safety of traditional East Asian herbal medicines for the treatment of post-stroke constipation will be included in this study. The methodological qualities, including the risk of bias, will be evaluated using the Cochrane risk of bias assessment tool. After screening the studies, a meta-analysis of the RCTs will be performed, if possible., Results: This study is expected to generate high-quality evidence of the efficacy and safety of herbal medicines to treat post-stroke constipation., Conclusion: Our systematic review will provide evidence to determine whether herbal medicines can be effective interventions for patients with post-stroke constipation., Ethics and Dissemination: Ethical approval is not required, as this study was based on a review of published research. This review will be published in a peer-reviewed journal and disseminated electronically and in print., Trial Registration Number: Research registry reviewregistry1117., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Aegle marmelos L. (bael) is a fruit tree of Rutaceae family, widely grown all over the world. This plant is gaining popularity because of its nutrient-rich fruits and immense traditional medicinal usage and pharmacological properties. The health promotive and protective effect of bael fruit is accounted by fibers, carotenoids, phenolics, terpenoids, coumarins, flavonoids, and alkaloids. The curative relevance of these compounds has been assessed by various in vivo and in vitro studies. Fruit shows numerous possible health benefits, namely, radio-protective effects, peroxidation, antibacterial, inhibition of lipid, antidiarrheal, gastroprotective, antiviral, antidiabetic, anti-ulcerative colitis, cardioprotective, free-radical scavenging (antioxidant) and hepatoprotective effects. The health benefits of bael are not only limited to edible portion (fruit), but it also extends to nonedible portion (root, trunk, bark, leaf, flower and seed) having comparable biologically active compounds. Increasing awareness about the role of diet among health-conscious consumers for human well-being has increased the interest in functional foods thereby exploration of the functional attributes of various underutilized plants is being reaffirmed and various sources are emerged out as suitable food material for processing industry. The various scientific reports collected from different bibliometric sources suggested that A. marmelos and its bioactive constituents could play a vital role in the prevention of several chronic and degenerative diseases associated with oxidation stress. This review emphasis on recent scientific evidences on nutrition and bioactive profile of A. marmelos, health benefits along with clinical and nonclinical trials of various phytoconstituents and A. marmelos potential in food processing industry for various food products. Our study suggests that this plant does indeed have pharmacological properties of interest, however, further extensive research is needed to establish a potential strategy that can balance the pharmacological and toxic effects of bael., (© 2020 John Wiley & Sons Ltd.)

This opinion commentary on the coronavirus disease 2019 (COVID-19) pandemic brings together observations from Zimbabwe specifically, and Africa broadly, drawing from the fields of pharmacogenomics, precision herbal medicine, and responsible innovation so as to respond to the pandemic in ways that are efficient, critically informed, principled, and responsive to needs in rural and urban communities across Africa. With new findings suggesting that COVID-19 is a systemic disease, impacting the respiratory system and beyond in some individuals, we need new molecular targets for therapeutics innovation more than ever. We argue that the current pandemic will likely strip the limited resources from other diseases such as malaria, human immunodeficiency virus (HIV) infection, and among others affecting the African continent. Hence, we need to address not only COVID-19 but also its broader health care and societal impacts in Africa. Extensive diagnostic testing to trace and isolate the COVID-19 cases as well as basic income and economic support for those who are unable to work will be needed. A critically informed and democratic governance that builds on transparency and trust for the elected leaders is crucial. Finally, the pandemic offers a silver lining for Africa: the prospects to integrate omics research with long-standing expertise in herbal medicine in Africa, thus accelerating the advances toward novel molecular therapeutic targets for COVID-19 and precision herbal medicine worldwide.

The current COronaVIrus Disease 19 (COVID-19) pandemic caused by SARS-CoV-2 infection is enormously affecting the worldwide health and economy. In the wait for an effective global immunization, the development of a specific therapeutic protocol to treat COVID-19 patients is clearly necessary as a short-term solution of the problem. Drug repurposing and herbal medicine represent two of the most explored strategies for an anti-COVID-19 drug discovery. Clove ( Syzygium aromaticum L.) is a well-known culinary spice that has been used for centuries in folk medicine in many disorders. Interestingly, traditional medicines have used clove since ancient times to treat respiratory ailments, whilst clove ingredients show antiviral and anti-inflammatory properties. Other interesting features are the clove antithrombotic, immunostimulatory, and antibacterial effects. Thus, in this review, we discuss the potential role of clove in the frame of anti-COVID-19 therapy, focusing on the antiviral, anti-inflammatory, and antithrombotic effects of clove and its molecular constituents described in the scientific literature.

Pyrrolizidine alkaloids (PAs) are a class of natural toxins with hepatotoxicity, genotoxicity and carcinogenicity. They are endogenous and adulterated toxic components widely found in food and herbal products. In this study, a sensitive and efficient ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was used to detect the PAs in 386 kinds of Chinese herbal medicines recorded in the Chinese Pharmacopoeia (2020). The estimated daily intake (EDI) of 0.007 μg/kg body weight (bw)/day was adopted as the safety baseline. The margin of exposure (MOE) approach was applied to evaluate the chronic exposure risk for the genotoxic and carcinogenic potential of PAs. Results showed that PAs was detected in 271 out of 386 samples with a content of 0.1-25,567.4 μg/kg, and there were 20 samples with EDI values above the baseline, 0.007 μg/kg bw/day. Beyond that, the MOE values for 10 out of 271 positive samples were below 10,000. Considering the actual situation, Haber's rule was used to assume two weeks exposure every year during lifetime, and still the MOE values for four out of 271 positive samples were under 10,000, indicating these products may have potential health risk. The developed method was successfully applied to detect the PAs-containing Chinese herbal medicines. This study provides convincing data that can support risk management actions in China and a meaningful reference for the rational and safe use of Chinese herbal medicines.

Sophora flavescens , also known as Kushen, has traditionally been used as a herbal medicine. In the present study we evaluated the ameliorative effects of kushenol C (KC) from S. flavescens against tBHP (tert-Butyl hydroperoxide)-induced oxidative stress in hepatocellular carcinoma (HEPG2) cells and acetaminophen (APAP)-induced hepatotoxicity in mice. KC pretreatment protected the HEPG2 cells against oxidative stress by reducing cell death, apoptosis and reactive oxygen species (ROS) generation. KC pretreatment also upregulated pro-caspase 3 and GSH (glutathione) as well as expression of 8-Oxoguanine DNA Glycosylase (OGG1) in the HEPG2 cells. The mechanism of action was partly related by KC's activation of Akt (Protein kinase B (PKB)) and Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) in the HepG2 cells. In in vivo investigations, coadministration of mice with KC and APAP significantly attenuated APAP-induced hepatotoxicity and liver damage, as the serum enzymatic activity of aspartate aminotransferase and alanine aminotransferase, as well as liver lipid peroxidation and cleaved caspase 3 expression, were reduced in APAP-treated mice. Coadministration with KC also up-regulated antioxidant enzyme expression and prevented the production of proinflammatory mediators in APAP-treated mice. Taken together, these results showed that KC treatment has potential as a therapeutic agent against liver injury through the suppression of oxidative stress.