Cancer is a major disease with ever-increasing morbidity and mortality. The metabolites derived from traditional Chinese medicine (TCM) have played a significant role in combating cancers with curative efficacy and unique advantages. Ferroptosis, an iron-dependent programmed death characterized by the accumulation of lipid peroxide, stands out from the conventional forms of cell death, such as apoptosis, pyroptosis, necrosis, and autophagy. Recent evidence has demonstrated the potential of TCM metabolites targeting ferroptosis for cancer therapy. We collected and screened related articles published in or before June 2023 using PubMed, Google Scholar, and Web of Science. The searched keywords in scientific databases were ferroptosis, cancer, tumor, traditional Chinese medicine, botanical drugs, and phytomedicine. Only research related to ferroptosis, the metabolites from TCM, and cancer was considered. In this review, we introduce an overview of the current knowledge regarding the ferroptosis mechanisms and review the research advances on the metabolites of TCM inhibiting cancer by targeting ferroptosis.

Background: Natural products are widely used for primary insomnia (PI). This systematic review with trial sequential analysis (TSA) aimed to summarize evidence pertaining to the effectiveness and safety of Zao Ren An Shen (ZRAS) prescription, a commercial Chinese polyherbal preparation, for treating PI. Methods: Controlled clinical trials appraising ZRAS compared to controls or as an add-on treatment were systematically searched across seven databases until January 2024. Cochrane ROB 2.0 and ROBINS-I tools were adopted to determine risk of bias. Quality of evidence was assessed using the GRADE framework. Results: We analyzed 22 studies, involving 2,142 participants. The effect of ZRAS in reducing Pittsburgh Sleep Quality Index scores was found to be comparable to benzodiazepines [MD = 0.39, 95%CI (-0.12, 0.91), p = 0.13] and superior to Z-drugs [MD = -1.31, 95%CI (-2.37, -0.24), p = 0.02]. The addition of ZRAS to hypnotics more significantly reduced polysomnographically-recorded sleep onset latency [MD = -4.44 min, 95%CI (-7.98, -0.91), p = 0.01] and number of awakenings [MD = -0.89 times, 95%CI (-1.67, -0.10), p = 0.03], and increased total sleep time [MD = 40.72 min, 95%CI (25.14, 56.30), p < 0.01], with fewer adverse events than hypnotics alone. TSA validated the robustness of these quantitative synthesis results. However, the quality of evidence ranged from very low to low. The limited data available for follow-up did not support meta-synthesis. Conclusion: While ZRAS prescription shows promising effectiveness in treating PI, the overall quality of evidence is limited. Rigorously-designed randomized control trials are warranted to confirm the short-term efficacy of ZRAS and explore its medium-to-long-term efficacy. Systematic Review Registration: (https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=471497), identifier (CRD42023471497).

Background and objectives: As microbes are developing resistance to antibiotics, natural, botanical drugs or traditional herbal medicine are presently being studied with an eye of great curiosity and hope. Hence, complementary and alternative treatments for uncomplicated pelvic inflammatory disease (uPID) are explored for their efficacy. Therefore, this study determined the therapeutic efficacy and safety of Sesamum indicum Linn seeds with Rosa damascena Mill Oil in uPID with standard control. Additionally, we analyzed the data with machine learning. Materials and methods: We included 60 participants in a double-blind, double-dummy, randomized standard-controlled study. Participants in the Sesame and Rose oil group (SR group) (n = 30) received 14 days course of black sesame powder (5 gm) mixed with rose oil (10 mL) per vaginum at bedtime once daily plus placebo capsules orally. The standard group (SC), received doxycycline 100 mg twice and metronidazole 400 mg thrice orally plus placebo per vaginum for the same duration. The primary outcome was a clinical cure at post-intervention for visual analogue scale (VAS) for lower abdominal pain (LAP), and McCormack pain scale (McPS) for abdominal-pelvic tenderness. The secondary outcome included white blood cells (WBC) cells in the vaginal wet mount test, safety profile, and health-related quality of life assessed by SF-12. In addition, we used AdaBoost (AB), Naïve Bayes (NB), and Decision Tree (DT) classifiers in this study to analyze the experimental data. Results: The clinical cure for LAP and McPS in the SR vs SC group was 82.85% vs 81.48% and 83.85% vs 81.60% on Day 15 respectively. On Day 15, pus cells less than 10 in the SR vs SC group were 86.6% vs 76.6% respectively. No adverse effects were reported in both groups. The improvement in total SF-12 score on Day 30 for the SR vs SC group was 82.79% vs 80.04% respectively. In addition, our Naive Bayes classifier based on the leave-one-out model achieved the maximum accuracy (68.30%) for the classification of both groups of uPID. Conclusion: We concluded that the SR group is cost-effective, safer, and efficacious for curing uPID. Proposed alternative treatment (test drug) could be a substitute of standard drug used for Female genital tract infections.

Although there have been significant advances in the treatment of heart failure in recent years, chronic heart failure remains a leading cause of cardiovascular disease-related death. Many studies have found that targeted cardiac metabolic remodeling has good potential for the treatment of heart failure. However, most of the drugs that increase cardiac energy are still in the theoretical or testing stage. Some research has found that botanical drugs not only increase myocardial energy metabolism through multiple targets but also have the potential to restore the balance of myocardial substrate metabolism. In this review, we summarized the mechanisms by which botanical drugs (the active ingredients/formulas/Chinese patent medicines) improve substrate utilization and promote myocardial energy metabolism by activating AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptors (PPARs) and other related targets. At the same time, some potential protective effects of botanical drugs on myocardium, such as alleviating oxidative stress and dysbiosis signaling, caused by metabolic disorders, were briefly discussed.

Phosphodiesterase-5 inhibitors (PDE5-i) have been widely used in clinical practice for the treatment of erectile dysfunction (ED). However, due to its suboptimal therapeutic effects and side effects, it is necessary to develop new medicines for ED treatment. Botanical drugs have been widely investigated as potential ED treatment drugs and have shown promising therapeutic effects. This review summarized 34 studies, including five botanical drugs with PDE5 inhibitory activity, seven botanical drugs without PDE5 inhibitory activity, and six mixed botanical drugs. The results of clinical studies regarding the aforementioned botanical drugs and relevant mechanisms are summarized in this study. It is necessary to conduct high-quality clinical trials to verify the dosage, targeted patients and therapeutic effects, and further pharmacology experiments are also needed to identify the active compounds.

Background: The incidence of glycolipid metabolic diseases is extremely high worldwide, which greatly hinders people\'s life expectancy and patients\' quality of life. Oxidative stress (OS) aggravates the development of diseases in glycolipid metabolism. Radical oxygen species (ROS) is a key factor in the signal transduction of OS, which can regulate cell apoptosis and contribute to inflammation. Currently, chemotherapies are the main method to treat disorders of glycolipid metabolism, but this can lead to drug resistance and damage to normal organs. Botanical drugs are an important source of new drugs. They are widely found in nature with availability, high practicality, and low cost. There is increasing evidence that herbal medicine has definite therapeutic effects on glycolipid metabolic diseases. Objective: This study aims to provide a valuable method for the treatment of glycolipid metabolic diseases with botanical drugs from the perspective of ROS regulation by botanical drugs and to further promote the development of effective drugs for the clinical treatment of glycolipid metabolic diseases. Methods: Using herb*, plant medicine, Chinese herbal medicine, phytochemicals, natural medicine, phytomedicine, plant extract, botanical drug, ROS, oxygen free radicals, oxygen radical, oxidizing agent, glucose and lipid metabolism, saccharometabolism, glycometabolism, lipid metabolism, blood glucose, lipoprotein, triglyceride, fatty liver, atherosclerosis, obesity, diabetes, dysglycemia, NAFLD, and DM as keywords or subject terms, relevant literature was retrieved from Web of Science and PubMed databases from 2013 to 2022 and was summarized. Results: Botanical drugs can regulate ROS by regulating mitochondrial function, endoplasmic reticulum, phosphatidylinositol 3 kinase (PI3K)/protein kinase B (AKT), erythroid 2-related factor 2 (Nrf-2), nuclear factor κB (NF-κB), and other signaling pathways to improve OS and treat glucolipid metabolic diseases. Conclusion: The regulation of ROS by botanical drugs is multi-mechanism and multifaceted. Both cell studies and animal experiments have demonstrated the effectiveness of botanical drugs in the treatment of glycolipid metabolic diseases by regulating ROS. However, studies on safety need to be further improved, and more studies are needed to support the clinical application of botanical drugs.

Objective: To systematically review the efficacy and safety of botanical drugs in the treatment of cancer-related fatigue (CRF) caused by gastric cancer (GC) and to determine the underlying pharmacological mechanisms using a network analysis. Methods: Databases such as China National Knowledge Infrastructure (CNKI), SinoMed, Wanfang, Pubmed, Embase, Cochrane Library, and Web of Science were searched for randomized controlled trials (RCTs) from inception to 18 April 2022. Methodological quality assessment was performed using the collaborative tool Cochrane, and data analysis were carried out using RevMan 5.4 and STATA 16 software. The botanical drugs with the highest frequency of use in the included studies was selected. The chemical composition, targets of action, disease targets, and shared targets of these botanical drugs were screened based on network analysis to explore the potential mechanisms of treating CRF in patients with gastric cancer (GC). Results: A total of 13 studies that included 986 patients with gastric CRF met the inclusion criteria. The results showed that botanical drugs could improve the CRF scores of gastric CRF, including the total scores of CRF dichotomous data [Odds Ratio (OR) = 4.22; 95% confidence interval (CI) 1.67-10.68; p = 0.002], the total scores of CRF continuous data [Standardized Mean Difference (SMD) = -0.98; 95% CI -1.36 to -0.60; p < 0.00001], the affective subscales of Piper Fatigue Scale (PFS) scores [Weighted Mean Difference (MD) = -0.79; 95%CI -0.92 to -0.65; p < 0.00001], the sensory subscales of PFS scores (MD = -0.57; 95%CI -0.77 to -0.37; p < 0.00001), the behavioral subscales of PFS scores (MD = -1.05; 95% CI -1.29 to -0.82; p < 0.00001), Quality of Life Questionnaire Core 30 (QLQ-C30) (MD = 10.53, 95% CI 8.26 to12.80; p < 0.00001), and the Karnofsky Performance Status scale (KPS) (MD = 5.18, 95% CI 2.60 to 7.76; p < 0.0001). The botanical drugs group had milder adverse effects than the control group. A total of 44 chemical components and 241 potential targets were obtained from the online database and 121 drug targets overlapped with the disease targets of CRF in patients with GC. Moreover, five key active ingredients, namely quercetin, Stigmasterol, luteolin, kaempferol, and isorhamnetin, as well as five key targets including AKT1, TP53, TNF, VEGFA, and CASP3, were screened. In addition, five key signaling pathways, including cancer, Hepatitis B, Prostate cancer, Hepatitis C, and Pancreatic cancer pathways, were obtained through enrichment analysis. Conclusion: The results of the study showed that botanical drugs have positive effects on CRF in patients with GC. However, more well-designed, multicenter, and large sample-sized Randomized Controlled Trials are required to evaluate the effectiveness of botanical drugs on CRF in patients with GC.

Chronic and unhealed wound is a serious public problem, which brings severe economic burdens and psychological pressure to patients. Various botanical drugs in traditional Chinese medicine have been used for the treatment of wounds since ancient time. Nowadays, multiple wound healing therapeutics derived from botanical drugs are commercially available worldwide. An increasing number of investigations have been conducted to elucidate the wound healing activities and the potential mechanisms of botanical drugs in recent years. The aim of this review is to summarize the botanical drugs in traditional Chinese medicine with wound healing properties and the underlying mechanisms of them, which can contribute to the research of wound healing and drug development. Taken together, five botanical drugs that have been developed into commercially available products, and 24 botanical drugs with excellent wound healing activities and several multiherbal preparations are reviewed in this article.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by erosive arthritis, which can involve multiple systems. Patients with RA may have a variety of comorbidities, including cardiovascular disease (CVD), lung cancer, lymphoma, infection, osteoporosis, fatigue, depression, colon cancer, breast cancer, prostate cancer, and Alzheimer\'s disease. Among these comorbidities, the incidence of CVD, lung cancer, lymphoma, infection, and osteoporosis is higher. CVD is a serious complication of RA. The risk of CVD and associated mortality rate in patients with RA is high, and the treatment rate is low. In addition to traditional risk factors, such as age, sex, blood pressure, and diabetes, RA is also associated with inflammation. Furthermore, therapeutic drugs for RA, including non-steroidal anti-inflammatory drugs, glucocorticoids, and disease-modifying anti-rheumatic drugs, have beneficial or harmful effects on cardiovascular events in patients with RA. This article discusses the effects of therapeutic drugs for RA on cardiovascular events.

Target identification of small molecules is an important and still changeling work in the area of drug discovery, especially for botanical drug development. Indistinct understanding of the relationships of ligand-protein interactions is one of the main obstacles for drug repurposing and identification of off-targets. In this study, we collected 9063 crystal structures of ligand-binding proteins released from January, 1995 to April, 2021 in PDB bank, and split the complexes into 5133 interaction pairs of ligand atoms and protein fragments (covalently linked three heavy atoms) with interatomic distance ≤5 Å. The interaction pairs were grouped into ligand atoms with the same SYBYL atom type surrounding each type of protein fragment, which were further clustered via Bayesian Gaussian Mixture Model (BGMM). Gaussian distributions with ligand atoms ≥20 were identified as significant interaction patterns. Reliability of the significant interaction patterns was validated by comparing the difference of number of significant interaction patterns between the docked poses with higher and lower similarity to the native crystal structures. Fifty-one candidate targets of brucine, strychnine and icajine involved in Semen Strychni (Mǎ Qián Zǐ) and eight candidate targets of astragaloside-IV, formononetin and calycosin-7-glucoside involved in Astragalus (Huáng Qí) were predicted by the significant interaction patterns, in combination with docking, which were consistent with the therapeutic effects of Semen Strychni and Astragalus for cancer and chronic pain. The new strategy in this study improves the accuracy of target identification for small molecules, which will facilitate discovery of botanical drugs.