Yi-Shen-Hua-Shi granule ameliorates diabetic kidney disease by the "gut-kidney axis".

ETHNOPHARMACOLOGICAL RELEVANCE: Yi-Shen-Hua-Shi (YSHS) granule is an effective prescription widely used in traditional Chinese medicine to treat diabetic kidney disease (DKD), its exact efficacy in treating DKD has been confirmed but the underlying regulatory mechanism has not been fully elucidated. AIM OF THE STUDY: To explore the mechanism by which YSHS granule regulates intestinal flora and serum metabolites and then regulates renal mRNA expression through the "gut-kidney axis", so as to improve DKD. MATERIALS AND METHODS: 40 rats were divided into five groups: Normal group (N) (normal saline), model group (M) (STZ + normal saline), YSHS granule low-dose group (YL) (STZ + 2.27 g kg-1 d-1), YSHS granule high-dose group (YH) (STZ + 5.54g kg-1 d-1) and valsartan group (V) (STZ + 7.38mg kg-1 d-1). After 6 weeks, changes in blood glucose, blood lipids, and renal function related indexes were observed, as well as pathological changes in the kidney and colon. Intestinal microbiota was sequenced by 16S rDNA, serum differential metabolites were identified by LC-MS/MS, and renal differences in mRNA expression were observed by RNA-seq. Further, through the association analysis of intestinal differential microbiota, serum differential metabolites and kidney differential mRNAs, the target flora, target metabolites and target genes of YSHS granule were screened and verified, and the "gut-metabolism-transcription" co-expression network was constructed. RESULTS: In group M, blood glucose, blood lipid and proteinuria were increased, inflammation, oxidative stress and renal function were aggravated, with the proliferation of mesangial matrix, vacuolar degeneration of renal tubules, accumulation of collagen and lipid, and increased intestinal permeability, and YSHS granule and valsartan improved these disorders to varying degrees. High dose of YSHS granule improved the diversity and abundance of flora, decreased the F/B value, greatly increased the abundance of Lactobacillus and Lactobacillus_murinus, and decreased the abundance of Prevoella UCG_001. 14 target metabolites of YSHS granule were identified, which were mainly enriched in 20 KEGG pathways, such as Glycerophospholipid metabolism, Sphingolipid metabolism and Phenylalanine, tyrosine and tryptophan biosynthesis. 96 target mRNAs of YSHS granule were also identified. The enriched top 20 pathways were closely related to glucose and lipid metabolism, of which a total of 21 differential mRNAs were expressed. Further correlation analysis revealed that Lactobacillus, Lactobacillus_murinus and Prevotella UCG_001 were highly correlated with Glycerophospholipid metabolism, Sphingolipid metabolism and Phenylalanine, tyrosine and tryptophan biosynthesis pathways. At the same time, 6 pathways including Glycerophospholipid metabolism, Arachidonic acid metabolism, Purine metabolism, Primary bile acid biosynthesis, Ascorbate and aldarate metabolism and Galactose metabolism were co-enriched by the target metabolites and the target mRNAs of YSHS granule, including 7 differential metabolites such as phosphatidylethanolamine and 7 differential genes such as Adcy3. The 7 differential metabolites had high predictive value of AUC, and the validation of 7 differential genes were highly consistent with the sequencing results. CONCLUSION: YSHS granule could improve DKD through the "gut-kidney axis". Lactobacillus and Lactobacillus_murinus were the main driving forces. 6 pathways related to glucose and lipid metabolism, especially Glycerophospholipid metabolism, may be an important follow-up response and regulatory mechanism.

Rapid evaluation of Radix Paeoniae Alba and its processed products by near-infrared spectroscopy combined with multivariate algorithms.

It is well known that the processing method of herbal medicine has a complex impact on the active components and clinical efficacy, which is difficult to measure. As a representative herb medicine with diverse processing methods, Radix Paeoniae Alba (RPA) and its processed products differ greatly in clinical efficacy. However, in some cases, different processed products are confused for use in clinical practice. Therefore, it is necessary to strictly control the quality of RPA and its processed products. Giving that the time-consuming and laborious operation of traditional quality control methods, a comprehensive strategy of near-infrared (NIR) spectroscopy combined with multivariate algorithms was proposed. This strategy has the advantages of being rapid and non-destructive, not only qualitatively distinguishing RPA and various processed products but also enabling quantitative prediction of five bioactive components. Qualitatively, the subspace clustering algorithm successfully differentiated RPA and three processed products, with an accuracy rate of 97.1%; quantitatively, interval combination optimization (ICO), competitive adaptive reweighted sampling (CARS), and competitive adaptive reweighted sampling combined with successive projections algorithm (CARS-SPA) were used to optimize the PLS model, and satisfactory results were obtained in terms of wavelength selection. In conclusion, it is feasible to use NIR spectroscopy to rapidly evaluate the effect of processing methods on the quality of RPA, which provides a meaningful reference for quality control of other herbal medicines with numerous processing methods.

[Between chemotherapies, herbalism and spiritualities: Anthropological study of therapeutic pluralism in adults with cancer in Mexico]. / Entre quimioterapias, herbolaria y espiritualidades. Estudio antropológico sobre el pluralismo terapéutico en adultos con cáncer en México.

OBJECTIVES: To analyze the characteristics of therapeutic pluralism in adult patients at a hospital Cancer Center, based on their health/illness/care-neglect trajectories. METHODS: Analytical-explanatory, ethnographic, transversal-applied qualitative study. Data was provided by ten participants with cancer treated at the Veracruz State Cancer Center. Ethnographic records, participant observation and semi-structured interviews were carried out using observational guides, semi-structured interview guides and hospital clinical records. Participants were identified with pseudonyms for privacy and confidentiality. RESULTS: Two main results were: 1) characterization of the diversity of therapies utilized by participants throughout their biographical trajectory related to their health/disease/care-neglect processes; 2) identification of the cultural characteristics involved in these complex processes of therapeutic plurality, closely related to the appearance of cancer. CONCLUSION: Sociocultural aspects are interwoven with emerging therapeutic pluralities in the complex disease processes in cancer. The implications of these factors in the health/disease/care-neglect processes in cancer are manifest even before the first symptoms, in daily actions of self-care and preventive care. The mixing of therapies is an effect of the globalization characteristic of capitalist societies, in which therapeutic pluralism becomes an optimal phenomenon for commercialization and consumption.

OBJETIVOS: Analizar las características del pluralismo terapéutico en torno al cáncer de adultos, atendidos en un hospital de cancerología, a partir de sus trayectorias de salud/enfermedad/atención-desatención. MÉTODOS: Estudio analítico-explicativo, etnográfico, transversal-aplicado y de carácter cualitativo. Se realizaron registros etnográficos, observación participante y entrevistas semiestructuradas. Para el artículo se tomaron los datos proporcionados por diez personas participantes con cáncer, atendidas en el Centro Estatal de Cancerología de Veracruz. La identificación de participantes se hará mediante seudónimos, para preservar la privacidad de datos personales. Los instrumentos de trabajo estuvieron conformados por guías de observación, guías de entrevistas semiestructuradas y expedientes clínicos del hospital mencionado. RESULTADOS: Se muestran dos resultados principales: 1) caracterización de la diversidad de terapias de acuerdo con las referencias de los participantes, y lo que utilizaron durante toda su trayectoria biográfica en torno a procesos salud/enfermedad/ atención-desatención; 2) identificación de los aspectos socioculturales que intervienen en estos procesos complejos de pluralidad terapéutica, estrechamente relacionados con la aparición del cáncer. CONCLUSIÓN: Los aspectos socioculturales están entretejidos con la pluralidad terapéutica emergente en los procesos complejos de la enfermedad del cáncer. La implicación de dichos factores en los procesos salud/enfermedad/atención-desatención al cáncer se manifiestan incluso antes de los primeros síntomas, es decir, en las acciones cotidianas del autocuidado y acciones de atención preventiva. El mestizaje terapéutico registrado da cuenta de los efectos de la globalización, característica de las sociedades capitalistas, en la que el pluralismo de terapias deviene en un fenómeno óptimo de comercialización y consumo.

Phytotherapy of mood disorders in the light of microbiota-gut-brain axis.

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.

Integrating herbal medicine into oncology care delivery: development, implementation, and evaluation of a novel program.

OBJECTIVE: To evaluate the feasibility of a novel program facilitating patient-provider communication about appropriate use of herbal medicine at a large academic cancer center and its impact on patient wellbeing. METHODS: In the Herbal Oncology Program (HOP), integrative medicine providers counseled patients about unmet symptom needs and prescribed traditional Chinese medicine (TCM) herbs when indicated, taking into consideration the clinical context, patient preference, and research evidence. To evaluate the feasibility and outcomes, we performed a retrospective analysis using medical record data (symptoms and other concerns that motivated patients to seek herbal products, types and numbers of dispensed TCM herbs, and demographic characteristics). We also conducted a survey to assess patient experience and satisfaction. RESULTS: All 851 participants were outpatients, with 712 (84%) in active treatment. HOP dispensed 1266 herbal prescriptions for a range of symptoms, most commonly GI symptoms (467, 37%); pain (353, 28%); and treatment-related fatigue, sleep, and mood disorders (346, 27%). Of 269 patients invited to the survey, 107 (40%) completed it. A majority of respondents 70.9% (73/103) were satisfied with the effectiveness of dispensed herbs in relieving their symptoms, and few 6.7% (7/104) had experienced mild adverse events that resolved after discontinuing herbal use. CONCLUSIONS: The study's findings support the feasibility of integrating herbal medicine into an academic oncology setting. Patient satisfaction with HOP was high, with limited adverse events. The patterns of herbal prescriptions in HOP suggest future areas for clinical research to strengthen the evidence base around safe and effective use.

Basics: A Review: In Situ Gel Dosage Forms for Herbal Medicine Delivery.

Herbal medicine is one of Indonesia's wealth with various indications that have been studied. Herbal medicine has accompanied human life from the past to the present with significant developments. With the use of manufacturing procedures such as nanotechnology, and formulations that alter the time and rate of drug release, referred to as modified release, various forms of herbal preparations have been developed, from conventional preparations to novelty preparations. Many herbal medicines have also been approved for market, and the manufacturing process also has a recognized standard. In this review, manual searches were carried out in electronic books and journals. Upon conclusion of the searches, gel in situ was discussed as an option for delivering herbal medicines, including formulas and evaluations to ensure the quality of the preparations. Poloxamers are one of the gelling agents that are widely used in thermo-responsive gel, followed by carbomers as pH-responsive gels, and sodium alginates as ion-responsive gels. Sol-to-gel changes can occur due to the presence of specific inducing agents present in the body according to the treatment target. This provides many advantages in terms of pharmacology, patient convenience, and the manufacturing process.

Prevalence, predictors and pregnancy outcomes of unprescribed and herbal medicine use in Ibadan, Nigeria.

BACKGROUND: Unprescribed and herbal medicines use among pregnant women is a public health concern in low and middle-income countries because of the potential teratogenic effects, insufficient safety and weak drug regulatory systems. Unprescribed and herbal medicines are common among pregnant women in Nigeria, and only a few researchers have documented the prevalence and the risk factors. However, evidence on the associated pregnancy outcomes is still lacking. We assessed the prevalence, predictors and pregnancy outcomes of unprescribed and herbal medicines use among pregnant women in Ibadan, Nigeria. METHODS: This study was a component of the Ibadan Pregnancy Cohort Study, a prospective cohort study, among pregnant women in Ibadan, Nigeria, who were enrolled at ≤ 20 weeks gestation at their first antenatal visit and followed up till delivery. In all, 571 women participated in the maternal drug use assessment during the third trimester using a pretested interviewer-administered questionnaire. The primary outcomes were unprescribed and herbal medicines use and pregnancy outcomes, secondary outcomes, were abstracted from medical records. The predictors assessed included sociodemographic, obstetric, antenatal care utilization, and lifestyle characteristics. Bi-variate logistic and Poisson regression analyses were used to evaluate the predictors and relative risk for the pregnancy outcomes of unprescribed and herbal medicines at 5% significance. RESULTS: The prevalence of unprescribed and herbal medicine use was 31.9% and 21.7%, respectively. On bivariate analysis, the significant predictors of unprescribed medicine (which were protective) were tertiary education, increasing income, adequate antenatal care (≥ 4 visits), and at least two doses of sulfadoxine-pyrimethamine. However, high parity and having an antenatal admission increased the risk. However, after adjusting for confounders, the significant factors associated with unprescribed medicines were; tertiary education (AOR) = 0.23; 95% CI: (0.06 - 0.95); p-value: 0.043] and obtaining at least two doses of sulfadoxine-pyrimethamine [AOR = 0.33; 95% CI: (0.29 - 3.60); p-value: 0.048]. For herbal medicines, the predictors were similar to unprescribed drugs. However, after adjusting for confounders, none was significant for herbal medicines. Unprescribed and herbal medicines were not significantly associated with pregnancy outcomes. CONCLUSIONS: Unprescribed and herbal medicines use were common among pregnant women in Ibadan, Nigeria, particularly among women with low economic status and those with poor utilization of antenatal care services. These significant predictors can be targeted for public health intervention. Specifically, health education that discourages the use of unprescribed and herbal medications to pregnant women during antenatal care.

Assessing knowledge of herbal medicine course for dental students.

BACKGROUND: The aims of this article are to assess dental students' knowledge about herbal medicine usage and the potential benefits and side effects, and to conduct a short course about herbal medicine. METHODS: All fourth-year pre-doctoral students were invited to participate in a herbal medicine course as a test while the sixth-year students were the control group. A survey was tested for validity and reliability. It comprised of 16 multiple choice questions was given before the course and one month after the course. The sum score of knowledge for each participant was calcuated based on the ability to identify the use of herbs in dentistry with high-quality evidence (correct answer) or total answer for periodontal disease and caries. RESULTS: The response rate for completing the study was 112 fourth-year students (73.7%) and 64 sixth-year students (39.0%). More than half of the participants (52.5%) were unsure about the importance of herbal medicine in dentistry. However, the majority also stated that the most common herbs used in dentistry were clove (62.9%), followed by curcuma turmeric (54.7%) and meswak (43.0%). The fourth-year students displayed evidence of a higher overall knowledge score after the course in herbal medicine related to periodontal disease in total and correct answers (mean 4.48 ± 4.13, 3.73 ± 3.31, respectively) compared to before the course (mean 0.84 ± 1.23, 0.74 ± 1.16, respectively) (p-value < 0.001). The post-course periodontal disease total and correct answers were statistically significant between fourth- and sixth-year students. CONCLUSION: Herbal medicine has a potential positive impact on dentistry. However, these effects are not fully investigated and received full attention in academic institute. This short educational program related to medicinal herbs can improve the knowledge of dental students. This will help increase the awareness about the use and potential side effects of herbal medicine in the dental field.

Efficacy and safety of anti-obesity herbal medicine focused on pattern identification: A systematic review and meta-analysis.

BACKGROUND: Herbal medicine based on pattern identification (PI) is used widely in Traditional Chinese Medicine. Proper herbal medicine based on PI has been suggested for effective weight reduction and decreasing the adverse events. This systematic review examined the effectiveness and safety of herbal medicine, focusing on PI in treating obesity. METHODS: Eight electric databases were used for searching randomized controlled trials (RCT) (to August 31, 2021). RCTs which prescribed herbal medicine to obese patients based on PI were included. Body weight (BW) and body mass index (BMI) were the primary outcomes. The risk of bias was assessed using Cochrane risk of bias tool, and the meta-analysis was conducted. Grading the evidence was conducted by using GRADEpro. RESULTS: Sixteen RCTs (1052 patients) were included: 2 studies compared herbal medicine to placebo (128 patients); 2 studies compared them to western medication (161 patients); 12 studies compared them with usual care (763 patients). The meta-analysis showed that the herbal formulas reduced the BW and BMI without significant Adverse events compared to the control group (BW: mean difference  = -4.10, 95% confidence interval: -5.14 to -3.06, I2 = 2% and BMI: mean difference = -1.53, 95% confidence interval: -1.88 to -1.19, I2 = 25%). Moderate-quality evidence on the primary outcomes was found. CONCLUSIONS: Herbal medicine - has good clinical efficacy and safety in treating obesity. This study has limitations that some literatures with high risk of bias in blinding or without using a standardized diagnosis of PI were included. However, the current evidence suggests the possibility of precision medicine using PI.

Traditional Herbal Medicine: A Potential Therapeutic Approach for Adjuvant Treatment of Non-small Cell Lung Cancer in the Future.

Lung carcinoma is the primary reason for cancer-associated mortality, and it exhibits the highest mortality and incidence in developed and developing countries. Non-small cell lung cancer (NSCLC) and SCLC are the 2 main types of lung cancer, with NSCLC contributing to 85% of all lung carcinoma cases. Conventional treatment mainly involves surgery, chemoradiotherapy, and immunotherapy, but has a dismal prognosis for many patients. Therefore, identifying an effective adjuvant therapy is urgent. Historically, traditional herbal medicine has been an essential part of complementary and alternative medicine, due to its numerous targets, few side effects and substantial therapeutic benefits. In China and other East Asian countries, traditional herbal medicine is increasingly popular, and is highly accepted by patients as a clinical adjuvant therapy. Numerous studies have reported that herbal extracts and prescription medications are effective at combating tumors. It emphasizes that, by mainly regulating the P13K/AKT signaling pathway, the Wnt signaling pathway, and the NF-κB signaling pathway, herbal medicine induces apoptosis and inhibits the proliferation and migration of tumor cells. The present review discusses the anti-NSCLC mechanisms of herbal medicines and provides options for future adjuvant therapy in patients with NSCLC.

Herbal medicine and acupuncture relieved progressive bulbar palsy for more than 3 years: A case report.

RATIONALE: Progressive bulbar palsy (PBP) is a type of motor neuron disease (MND). The main symptoms include dysarthria, dysphagia, tongue muscle atrophy and fasciculations. This disease is generally severe and develops rapidly. Due to the lack of effective treatment, many patients with MND in China turn to traditional Chinese medicine treatment for help. We successfully relieved dysphagia and sialorrhea in a patient with PBP for 3 years with herbal medicine and acupuncture. PATIENT CONCERNS: The patient was a 68-years-old woman with PBP and suffered from severe dysphagia and sialorrhea. DIAGNOSES: Progressive bulbar palsy. INTERVENTIONS: Chinese herbal medicine and acupuncture. OUTCOMES: After 4 months of herbal medicine and acupuncture treatment, dysphagia and sialorrhea were relieved considerably. The patient's condition has been stable for more than 3 years and continues to be treated with Chinese herbal medicine and acupuncture. LESSONS: Our case suggests that alternative therapies such as herbal medicine and acupuncture may be effective in alleviating the symptoms of MND/PBP. However, standardized clinical studies are still required to verify the effectiveness and safety.

Opportunities and hurdles to European market access for multi-herbal traditional Chinese medicine products: An analysis of EU regulations for combination herbal medicinal products.

TCM herbal remedies are popular among European patients. However, a very limited number of TCM products have been approved as herbal medicinal products (HMPs) in Europe. Multi-herbal TCM products, the most prevalent form of medication in TCM practice, are even rare. This indicates multi-herbal TCM products are facing considerable obstacles in the access to EU market. To further identify such obstacles, we make a systematic analysis of current advances in both EU herbal monographs and combination HMPs granted in member states and present main features of the regulation as well as challenges for multi-herbal TCM products. The results show the EU is open to combination HMPs based on TCM or other non-European traditions. The regulation allows appropriate flexibility in the range of drug extraction rations, variation in concentrations of extraction solvent and number of herbal drugs presented in the product, if plausible pharmacological effects could be justified. Meanwhile, to guarantee the safety and efficacy based on medicinal usage, especially to justify the rationale or plausibility of the combination, is the key element for well-established use or traditional use combination HMPs. Additionally, EU herbal monographs also have great value in their marketing procedure. Nonetheless, there are many challenges in the European market access of multi-herbal TCM products which lies in quality control, safety and efficacy evaluation and others e.g., practical standard for full marketing authorization. Enforced scientific research and communication among research institutions, industries and authorities are necessary to further facilitate the access of multi-herbal TCM products to EU market. The results of this article may provide guidance for HMPs based on TCM or other non-European traditions with intention to entering EU market.

Development of Highly Sensitive Method for Sugar Determination in Herbal Medicine; Application of Monosaccharides and Oligosaccharides in Japanese Angelica Root and Rehmannia Root.

We have developed a simple and accurate method for quantifying sugars in herbal medicines, which have hitherto been difficult to quantify. Using ultra performance liquid chromatography-quadrupole-time-of-flight (UPLC-Q-TOF)-MS and two types of columns with different chemical properties, we determined the optimum conditions for separating nine sugars (fructose, galactose, glucose, mannitol, sucrose, melibiose, raffinose, manninotriose, and stachyose) commonly found in herbal medicines. Separation was completed within 10 min when an apHera NH2 HPLC column was used, although galactose and glucose could not be separated. On the other hand, the nine sugars were completely separated within 16 min when a hydrophilic interaction chromatography (HILIC)pak VG-50 2D column was used. The calibration curves obtained using those two columns gave good linearity for the sugar standards, and the coefficient of determination was 0.995 or higher. Both columns showed excellent performance with short analysis time and high sensitivity. Using our developed method, we were able to quantify sugars in galactose-free herbal medicines within 10 min and in herbal medicines containing galactose within 16 min. We revealed that our method could be used for the analysis of sugars in Angelica acutiloba and Rehmannia glutinosa roots.

The effects of beliefs, knowledge, and attitude on herbal medicine use during the COVID-19 pandemic: A cross-sectional survey in Indonesia.

Background: Herbal medicines are gaining a greater degree of popularity as complementary and alternative medicines during the COVID-19 pandemic. Nonetheless, there is a lack of data concerning the rationale for and factors influencing their use. Methods: A cross-sectional community-based online study involving 1,621 participants was conducted to explore the effects of magical health beliefs, holistic health beliefs, knowledge, and pro- complementary alternative medicine (CAM) attitudes on herbal medicine use in the Indonesian population. Results: Logistic regression findings showed that knowledge about herbal medicines was independently and positively associated with herbal medicine use to a greater extent than herbal medicine non-use (adjusted odds ratio; AOR = 1.20; 95% confidence interval; CI = 1.16 to 1.24). The participants who used herbal medicines had a greater magical health belief score than herbal medicine non-users, with AOR = 1.03 and 95% CI = 1.00 to 1.06. Moreover, holistic health beliefs and pro-CAM attitudes were also found to be independently associated with herbal medicine use. Conclusion: Magical health beliefs, holistic health belief, knowledge, and attitudes are key factor in determining the herbal medicine use. Our findings offer crucial implications for health policymakers to encourage the use of herbal medicine during the COVID-19 pandemic.

Development of the Korean Medicine Core Outcome Set for Primary Dysmenorrhea (COS-PD-KM) for Herbal Medicine Treatment of Primary Dysmenorrhea in Primary Clinics.

The aim of this study was to develop a Korean medicine (KM) core outcome set (COS) for primary dysmenorrhea to evaluate the effectiveness of herbal medicine (HM) in treating primary dysmenorrhea in patients visiting KM primary clinics. Previously reported outcomes were identified through a literature review to define outcomes and effect modifiers (EMs) for the questionnaire. Experts were invited to conduct modified Delphi consensus exercises, and primary care clinicians were invited to conduct Delphi consensus exercises to evaluate suitability and feasibility. Finally, an additional round of a modified Delphi exercise was conducted with experts to obtain a final agreement on the COS. Seventeen outcomes and 15 EMs were included from a literature review, and one effect modifier was suggested by the experts (Phase 1). In Phase 2, after the modified Delphi consensus exercises by experts, 10 outcomes and 11 EMs were included in the COS. The clinicians all agreed on the feasibility of COS (Phase 3). Finally, 10 outcomes and 6 EMs were included in the COS-PD-KM after the final modified Delphi consensus exercise (Phase 4). The effectiveness of HM used in primary clinics could be evaluated with this COS in patients with primary dysmenorrhea. Further studies that involve more relevant stakeholder groups, such as patient representatives and gynecological experts, are needed.

Potential Focal Adhesion Kinase Inhibitors in Management of Cancer: Therapeutic Opportunities from Herbal Medicine.

Focal adhesion kinase (FAK) is a multifunctional protein involved in cellular communication, integrating and transducing extracellular signals from cell-surface membrane receptors. It plays a central role intracellularly and extracellularly within the tumor microenvironment. Perturbations in FAK signaling promote tumor occurrence and development, and studies have revealed its biological behavior in tumor cell proliferation, migration, and adhesion. Herein we provide an overview of the complex biology of the FAK family members and their context-dependent nature. Next, with a focus on cancer, we highlight the activities of FAK signaling in different types of cancer and how knowledge of them is being used for screening natural compounds used in herbal medicine to fight tumor development.

A Review of Herbal Medicine-Based Phytochemical of Garcinia as Molecular Therapy for Breast Cancer.

Data from globocan statistic in 2020 indicate that breast cancer has become highest incidence rate of cancer. Estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) are known immunohistochemistry (IHC) markers that mediate cell growth and survival signaling. Furthermore, regulator proteins, receptors, and their downstream signaling pathways have emerged as critical components in breast cancer formation and proliferation, and have become well-established therapeutic targets and the core focus of breast cancer therapy research. Garcinia is a big genus in the Clusiaceae family that contains a wide spectrum of biologically active metabolites for the chemical composition of their isolated fruits, stem barks, seeds, leaves, and roots, have resulted including polyisoprenylated benzophenones, polyphenols, bioflavonoids, xanthones, lactones, and triterpenes. This review article aimed to analyze the potential of Garcinia phytochemicals as a molecular therapy of breast cancer. The results showed that phytochemicals of Garcinia (i.e., α-mangostin, Cambogin, Gambogic Acid [GA], Garcinol, Griffipavixanthone, Friedolanostane triterpenoid, Hexane, Neobractatin, 7-Epiclusianone, xanthochymol - guttiferone E, and isoxanthochymol - cycloxanthochymol) have anticancer properties, including apoptosis, inhibition of proliferation, and metastasis. This review is important to provide information regarding phytochemicals of Garcinia as an alternative treatment for breast cancer patients. This article selected 28 article researches based on inclusion criteria with the keyword "Garcinia" and "Breast cancer", in English, and available in full text and abstract searching on PubMed.

Gut Microbiome: The Interplay of an "Invisible Organ" with Herbal Medicine and Its Derived Compounds in Chronic Metabolic Disorders.

Resembling a concealed "organ" in a holobiont, trillions of gut microbes play complex roles in the maintenance of homeostasis, including participating in drug metabolism. The conventional opinion is that most of any drug is metabolized by the host and that individual differences are principally due to host genetic factors. However, current evidence indicates that only about 60% of the individual differences in drug metabolism are attributable to host genetics. Although most common chemical drugs regulate the gut microbiota, the gut microbiota is also known to be involved in drug metabolism, like the host. Interestingly, many traditional herbal medicines and derived compounds are biotransformed by gut microbiota, manipulating the compounds' effects. Accordingly, the gut microbiota and its specified metabolic pathways can be deemed a promising target for promoting drug efficacy and safety. However, the evidence regarding causality and the corresponding mechanisms concerning gut microbiota and drug metabolism remains insufficient, especially regarding drugs used to treat metabolic disorders. Therefore, the present review aims to comprehensively summarize the bidirectional roles of gut microbiota in the effects of herbal medicine in metabolic diseases to provide vital clues for guiding the clinical application of precision medicine and personalized drug development.

Silibinin: a toxicologist's herbal medicine?

Silymarin is an herbal remedy, commonly called milk thistle, or St. Mary's Thistle, and has been used for over 2000 years. It has been available as a capsule of the plant extract in Europe since 1974 to treat hepatic disorders. To date toxicologists have relied on animal studies, human case series, or retrospective reviews to decide on its use. In the U.S. the ability to use IV silibinin, its pharmacologically active purified flavonolignan, is hindered by its lack of availability as a Food and Drug Administration approved pharmaceutical preparation. This commentary reviews the in vitro studies, animal studies, and human retrospective analyses which form the basis for its clinical use. Despite the numerous publications, summarized in this issue in a systematic review, the mortality rate from Amanita mushroom ingestion remains stubbornly the same over four decades of use, and hovers around 10%. Although in the retrospective systematic review the use of silibinin, or penicillin, compared to routine care is statistically significantly superior when the primary outcome is fatality. Despite this there is no quality randomized trial to definitively demonstrate its utility. While, intravenous silibinin has a low toxicity, unanswered is whether it is useful in protecting the liver in cases of amanitin-containing mushrooms toxicity, and whether earlier administration would likely improve outcomes.

The draft genome and multi-omics analyses reveal new insights into geo-herbalism properties of Citrus grandis 'Tomentosa'.

Citrus grandis 'Tomentosa' (CGT) (Huajuhong, HJH) is a widely used medicinal plant, which is mainly produced in Guangdong and Guangxi provinces of South China. Particularly, HJH from Huazhou (HZ) county of Guangdong province has been well-regarded as the best national product for geo-herbalism. But the reasons for geo-herbalism property in HJH from HZ county remains a mystery. Therefore, a multi-omics approach was applied to identify the nature of the geo-herbalism in CGT from three different regions. The comprehensive screening of differential metabolites revealed that the Nobiletin content was significantly different in HZ region compared to other regions, and could be employed as a key indicator to determine the geo-herbalism. Furthermore, the high-quality genome (N50 of 9.12 Mb), coupled with genomics and transcriptomics analyses indicated that CGT and Citrus grandis are closely related, with a predicted divergence time of 19.1 million years ago (MYA), and no recent WGD occurred in the CGT, and the bioactive ingredients of CGT were more abundant than that of Citrus grandis. Interestingly, Nobiletin (Polymethoxyflavones) content was identified as a potential indicator of geo-herbalism, and O-methyltransferase (OMT) genes are involved in the synthesis of Polymethoxyflavones. Further multi-omics analysis led to the identification of a novel OMT gene (CtgOMT1) whose transient overexpression displayed significantly higher Nobiletin content, suggesting that CtgOMT1 was involved in the synthesis of Nobiletin. Overall, our findings provide new data resources for geo-herbalism evaluation, germplasm conservation and insights into Nobiletin biosynthesis pathways for the medicinal plant C. grandis 'Tomentosa'.