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Depression is a prevalent stress disorder, yet the underlying physiological mechanisms linking stress to appetite and weight loss remain elusive. While most antidepressants are associated with excessive weight and appetite gain, sertraline (SER) exhibits a lower risk of these side effects. Metacinnabar (β-HgS), the primary component of Tibetan medicine Zuotai, has been shown to enhance mice's resilience against external stress without causing excessive increases in weight or appetite. However, the precise physiological pathway through which β-HgS restores appetite and weight in stressed mice remains unclear. The objective of this study is to assess the efficacy of β-HgS in ameliorating weight loss and appetite suppression induced by pressure stimulation in mice, as well as elucidate its potential mechanisms of action. The present study employed chronic restraint stress (CRS) and chronic unpredictable mild stress (CUMS) as experimental models to simulate environmental stress encountered in daily life. Subsequently, a series of experiments were conducted, including behavior tests, HE staining of rectal and hippocampal pathological sections, detection of depression-related biological indicators, analysis of intestinal flora diversity, as well as metabolomics analysis of hippocampal and intestinal contents. Dysregulation of glycerophospholipid metabolism may represent the principal pathway underlying reduced appetite, body weight, neurotransmitter and appetite hormone levels, heightened inflammatory response, hippocampal and rectal tissue damage, as well as altered composition of intestinal microbiota in stressed mice. Following intervention with SER and β-HgS in stressed mice, the deleterious effects induced by stress can be ameliorated, in which the medium-dose β-HgS exhibited superior performance. The aforementioned research findings suggest that the stress-induced decrease in appetite and body weight in mice may be associated with dysregulation in glycerophospholipid metabolism connecting the gut-brain axis. β-HgS exhibits potential in ameliorating depressive-like symptoms in mice subjected to stress, while concurrently restoring their body weight and appetite without inducing excessive augmentation. Its therapeutic effect may also be attributed to its ability to modulate glycerophospholipid metabolism status and exert influence on the gut-brain axis. [Display omitted] [ABSTRACT FROM AUTHOR]

Andiroba seed oil (Carapa guianensis Aubl.) is widely used by traditional populations in tropical countries, especially in the Brazilian Amazon, because of its anti-inflammatory, antirheumatic, antiseptic, healing and antipyretic properties, among others, which makes it useful for the treatment, mainly, of skin afflictions and wounds. To describe the modulation of the immune system by andiroba oil (Carapa guianensis Aubl.) in inflammation and wound healing. A scoping review was performed, following the recommendations of the Joanna Briggs Institute (JBI) and PRISMA for Scoping Reviews (PRISMA-ScR). As inclusion criteria, in vitro , in vivo , ex vivo, and clinical studies were selected, in Portuguese, English, or Spanish, in thirteen databases of published studies, gray literature, and references of the included studies, which deal with immune modulation by andiroba oil in the context of the various therapeutic applications that make use of its anti-inflammatory and wound healing properties. The selection of information sources was carried out by two independent reviewers between November 2022 and January 2023. The process of data extraction and evidence analysis was conducted by four pairs of independent reviewers between January and February 2023. 22 sources of evidence were included in this scoping review, mostly scientific articles published between 2005 and 2021 with in vivo sampling. The evidence suggests that andiroba oil reduces inflammation and promotes the healing of wounds of multiple etiologies by reducing leukocyte infiltration, increasing phagocytic activity, enhancing interleukin and inflammatory cytokine activity, promoting fibroblast recovery, increasing growth factors, reducing apoptotic cells, promoting reepithelialization, as well as promoting angiogenesis, reducing edema, and stimulating the production of glucocorticoids that alleviate pain. Additionally, different formulations of the oil (such as nanoemulsions, films and gels) are more effective in modulating inflammation and wound healing compared to in natura oil. Evidence in the literature suggests that andiroba oil (Carapa guianensis Aubl.) has positive effects on immune modulation in inflammation and wound healing, which makes it a biocompound with high therapeutic potential. [Display omitted] • Andiroba oil (Carapa guianensis Aubl.) reduces inflammatory infiltrate in wounds and increases phagocyte activity. • Andiroba oil promotes wound healing and increases traction strength. • Andiroba oil systemically induces the production of glucocorticoids and reduces pain and severity of injuries. • Pure andiroba oil pure and its different presentations increase the effectiveness of inflammation, wound healing therapies. [ABSTRACT FROM AUTHOR]

Goiters are enlargements of the thyroid gland and are a global public issue. Quemeiteng granule (QMTG) is a traditional Chinese medicine (TCM) formula used to treat goiter in Yunnan Province. However, the effectiveness and underlying mechanism of these treatments have not been fully elucidated. This study aimed to investigate the therapeutic effects of QMTG on goiter and the downstream regulatory mechanisms. In this study, we first evaluated the antigoiter efficacy of QMTG through biochemical indices [body weight, thyroid coefficient, triiodothyronine (T3), thyroxine (T4), free triiodothyronine (FT3), free thyroxine (FT4), and thyroid stimulating hormone (TSH)] and hematoxylin-eosin (HE) staining in a Propylthiouracil (PTU)-induced model. Based on microRNA sequencing (miRNA-seq) and bioinformatics analysis, key miRNA was screened out. A dual-luciferase reporter assay was performed to confirm the transcriptional regulation of the target gene by the miRNA. The viability of rat thyroid microvascular endothelial cells (RTMECs) and human thyroid microvascular endothelial cells (HTMECs) was assessed using the CCK-8 assays. The migration and angiogenesis of RTMECs and HTMECs were visualized through tube formation and wound scratch assays. Proteins involved in angiogenesis and the ERK pathway were assessed via Western blotting. QMTG significantly increased body weight, decreased the thyroid coefficient, increased the levels of T3, T4, FT3 and FT4 and reduced TSH levels in rats with goiter. QMTG also promoted the morphological recovery of thyroid follicles. MiR-217-5p was identified as a key miRNA. Our studies revealed that miR-217-5p directly targets FGF2 and that QMTG promotes the recovery of thyroid hormone (TH) levels and morphological changes in the thyroid, suppresses thyroid microvascular endothelial cell vitality, tube formation and migration, and reduces the expression of VEGF, Ang-1 and VCAM-1 triggered by miR-217-5p, thereby inhibiting the Ras/MEK/ERK cascade through FGF2. Our experiments demonstrated that the QMTG had therapeutic effects on goiter. These effects were attributed to the inhibition of ERK pathway-induced proliferation and angiogenesis through the targeting of FGF2 by miR-217-5p. [Display omitted] [ABSTRACT FROM AUTHOR]

The roots of Asarum heterotropoides F. Maekawa var. mandshuricum F. Maekawa (AR) is a traditional herbal medicine used across Asia, including Korea, China, and Japan. AR exhibits a range of biological activities, such as anti-inflammatory, anti-cancer, cold treatment, and anti-nociceptive effects. Various extraction methods, including decoction, which utilizes traditional knowledge and techniques. The AR decoction extract expected to contain fewer toxicants and have reduced toxicity due to the use of hot water in the extraction process. However, scientific evidence on the toxicity of AR decoction extracts is lacking, necessitating further studies for safe usage. This study aimed to evaluate the genotoxicity and toxicity of single and repeated administration of AR decoction extracts. The genotoxicity was assessed using a bacterial reverse mutation (Ames test), an in vitro mammalian chromosome aberration test (CA test), and an in vivo micronucleus test (MN test) in Sprague-Dawley (SD) rats. The general toxicity was evaluated through single-dose and 13-week repeated-dose toxicity studies. In the single-dose toxicity study, 40 SD rats were orally administered AR decoction extract at doses of 1000, 2000, and 5000 mg/kg. In the 13-week repeated-dose toxicity study, 140 SD rats received daily oral doses of 0, 250, 500, 1000, 2000, and 5000 mg/kg of AR decoction extract. The genotoxicity tests revealed that AR decoction extract was not genotoxic. The single-dose toxicity study showed no changes in body weight, clinical pathology, or macroscopic findings, with the approximate lethal dose (ALD) exceeding 5000 mg/kg. The 13-week repeated-dose toxicity study demonstrated no treatment-related changes in body weight, general symptoms, hematology, clinical chemistry, or urinalysis. Histopathological findings revealed hyperplasia of squamous cells in the forestomach after AR decoction extract administration, a treatment-related effect that resolved during the recovery period. The no observed adverse effect level (NOAEL) for both male and female rats was estimated to be 2000 mg/kg. This study establishes the non-toxic dose of AR decoction extract, providing a foundation for further non-clinical and clinical evaluations AR safety. [Display omitted] • The roots of Asarum heterotropoides var. mandshuricum (AR) decoction extract does not induce genotoxicity. • The approximate lethal dose of the AR decoction extract was greater than 5000 mg/kg. • The NOAEL of AR decoction extract was 2000 mg/kg in both males and females. • AR decoction extract did not contain known toxicant found in AR powder. [ABSTRACT FROM AUTHOR]

Cataract is the most common cause of blindness worldwide, a visual disorder caused by a clouded lens that seriously affects People's Daily lives. Age-related cataract (ARC) is the most common type of cataract due to long-term combined effects of many factors, and its pathogenesis is varied. At present, the surgery is the main treatment for cataracts, but it is still limited to the prevention, treatment of early cataracts and the postoperative complications care. While, its drug treatments are still in the stage of exploration and research. Traditional Chinese Medicine (TCM), a unique resource in China, is conceived under the guidance of traditional Chinese medicine theory and has little toxicity and side effects, but it has made great progress in the treatment and prevention of ARC. This review presents an overview of the pathogenesis of ARC in both traditional and modern medicines and summarizes the history and therapeutic effect of TCM on ARC including their formula, crude drugs and active components, and also the other auxiliary methods. A number of recognized databases like SciFinder, PubMed, Science Direct, Google Scholar, and China National Knowledge Infrastructure (CNKI) were extensively explored by using keywords and phrases such as "cataract", "age-related cataract", "traditional medicine", "ethnopharmacology", "herbs", "medicinal plants", or other relevant terms, and the plants/phytoconstituents that are evaluated in the models of age-related cataract. As well as the current TCM adjuvant therapy used in the clinical treatment were summarized. TCM revealed to plays an active role in treating age-related cataract, via multi-pathway and multi-target, and can treat or delay ARC by inhibiting abnormal glucose metabolism, antioxidant damage, inhibiting LEC apoptosis, and so on, which is in concordance with the good effects of the global use of TCM in clinical application. Concerning the early prevention and treatment of cataract and postoperative complications, TCM and auxiliary methods remain to achieve better clinical effects. ARC belongs to the category of "Yuan Yi Nei Zhang" in TCM theory, showing that there are many causes of ARC including aging, and kidney-yang, spleen, sperm and blood deficiencies. At the same time, the viscera gradually decline, as well as yin or yang progressively become weak, especially in the elder people. So, TCM could be mainly based on liver, kidney, and spleen syndrome differentiation, personalizing diagnosis and treatment, following multiple targets, regulating fundamentally yin and yang, and thus justifying the advantages of Chinese medicine in the prevention and treatment of ARC. [Display omitted] • This review presents an overview of the pathogenesis of Age-Related Cataract in both modern and traditional medicines. • The review summarizes the therapeutic effect of traditional Chinese medicine on Age-Related Cataract. • The purpose of this review is to carry forward the advantages of traditional Chinese medicine treatment based on syndrome differentiation, putting people and lives first. [ABSTRACT FROM AUTHOR]

Promoting the recovery of cerebral blood circulation after cerebral infarction (CI) is an important intervention. Buyang Huanwu decoction (BHD) is a classic prescription for treating CI that promotes angiogenesis. Cytoplasmic glycolysis ischaemic-region cells after CI may be highly activated to maintain metabolic activity under hypoxia. From the perspective of long-term maintenance of glycolytic metabolism in the ischaemic area after CI, it may be beneficial to promote angiogenesis and maintain glial cell activation and neuronal survival. In this context, the regulatory relationship of lncRNAs and miRNAs with mRNAs is worthy of attention. Mining the competitive binding relationships among RNAs will aid in the screening of key gene targets post-CI. In this study, network pharmacology and bioinformatics were used to construct a ceRNA network, screen key targets, and explore the effect of glycolysis on angiogenesis during BHD-mediated CI regulation. This study aimed to explore the effect of BHD on angiogenesis after glycolysis regulation in CI. According to the 21 active BHD ingredients we identified by our research team, we conducted network pharmacology. BHD targets that can regulate glycolysis and angiogenesis after CI were screened from the GeneCards, CTD and OMIM databases. We retrieved CI-related datasets from the GEO database and screened for differentially expressed lncRNAs and miRNAs. LncRNA‒miRNA–mRNA/TF targeting relationships were screened and organized with the miRcode, miRDB, TargetScan, miRWalk, and TransmiR v2.0 databases. Cytoscape was used to construct an lncRNA‒miRNA–mRNA/TF ceRNA network. Through BioGPS, key mRNAs/TFs in the network were screened for enrichment analysis. Animal experiments were then conducted to validate some key mRNAs/TFs and enriched signalling pathways. PFKFB3 and other genes may help regulate glycolysis and angiogenesis through AMPK and other signalling pathways. The anti-CI effect of BHD may involve maintaining activation of genes such as AMPK and PFKFB3 in the ischaemic cortex, maintaining moderate glycolysis levels in brain tissue, and promoting angiogenesis. BHD can regulate glycolysis and promote angiogenesis after CI through multiple pathways and targets, in which AMPK signalling pathway activation may be important. [Display omitted] • Glycolysis is the main energy source of angiogenesis after cerebral infarction. • BHD regulates glycolysis and promotes angiogenesis after cerebral infarction. • BHD promotes angiogenesis may be related to the maintenance of AMPK activation. [ABSTRACT FROM AUTHOR]

Erigeron breviscapus is a common medicine of eight ethnic minorities, including Miao, Naxi, and Yi. As early as the Ming Dynasty (AD 1368–1644), Lanmao's Materia Medica of Southern Yunnan (AD 1436) recorded that the medicine is used for the treatment of "Zuo tan you huan." In modern pharmacological research, Erigeron breviscapus injection is the most commonly used preparation in the treatment of ischemic stroke caused by acute cerebral infarction, but its mechanism of action in the treatment of ischemic stroke is not well understood. In this study, a metabonomics study based on ultraperformance liquid chromatography–quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS) was used in investigating the effect of a traditional Chinese medicine preparation Erigeron breviscapus injection on the rat model of focal cerebral ischemia-reperfusion and the affinity of its main components with the targets of mitochondrial apoptotic pathways. This study used molecular docking technology to verify the effective binding ability of main effective components of Erigeron breviscapus injection to target proteins related to mitochondrial apoptosis pathway. This study developed a metabonomics method based on the ultra-performance liquid chromatography combined with quadrupole time-of-flight tandem mass spectrometry (UPLC Q-TOF MS) to evaluate the efficacy and study the mechanism of traditional Chinese medicine preparation. With pattern recognition analysis (principal component analysis and partial least squares-discriminate analysis) of urinary metabolites, a clear separation of focal cerebral ischemia-reperfusion model group and healthy control group was achieved. Erigeron breviscapus injection can significantly reduce the area of cerebral infarction, improve tissue morphological lesion in rats, and can increase the number of Nissl bodies. It may be a promoting factor by inhibiting hippocampal nerve cell apoptosis and Bax protein expression and by exerting effects against ischemia reperfusion after the induction of apoptosis. Thus, it plays a role in brain protection. Moreover, it can considerably promote the recovery of neurological deficiency signs in advance. Meanwhile, Erigeron breviscapus decreased malondialdehyde content and T-NOS activity. Its curative effect from strong to weak order: low dose > high dose > medium dose. The representative components of Erigeron breviscapus have good affinity with the active sites of mitochondrial apoptosis-related proteins. Metabolomics found that the potential biomarkers regulated by breviscapine are kynurequinolinic acid, succinylornithine, and leucine proline. It is speculated that it may participate in TRP–kynurequinolinic acid and succinylornithine–urea cycle–NO metabolic pathways. This paper revealed the potential biomarkers and metabolic pathways regulated by Erigeron breviscapus. It was speculated that the mechanism is related to its inhibition of mitochondrion-mediated apoptosis. Erigeron breviscapus could restore the metabolic profiles of the model animals to normal animal levels. The mechanism may be related to the potential biomarkers of quinolinic acid, succinylornithine, and leucine proline and the metabolic pathways involved. However, the exact mechanism by which Erigeron breviscapus inhibits mitochondrion-mediated apoptosis remains to be further explored. [Display omitted] • The metabolic profile of cerebral ischemia-reperfusion injury model rats regulated by Breviscapus injection were revealed. • A new method of metabolomics combined with pharmacodynamics to evaluate the effectiveness of ethnomedicine was explored. • Erigeron breviscapus has high research value. • Erigeron breviscapus is a common medicine of eight ethnic minorities, such as the Miao, Naxi and Yi nationalities. [ABSTRACT FROM AUTHOR]

Stroke is one of the leading causes of death and disability. The only FDA-approved therapy for treating stroke is tissue plasminogen activator (tPA), exhibiting a short therapeutic window. Due to this reason, only a small number of patients can be benefitted in this critical period. In addition, the use of endovascular interventions may reverse vessel occlusion more effectively and thus help further improve outcomes in experimental stroke. During recovery of blood flow after ischemia, patients experience cognitive, behavioral, affective, emotional, and electrophysiological changes. Therefore, it became the need for an hour to discover a novel strategy for managing stroke. The drug discovery process has focused on developing herbal medicines with neuroprotective effects via modulating neuroplasticity. We gather and highlight the most essential traditional understanding of therapeutic plants and their efficacy in cerebral ischemia-reperfusion injury. In addition, we provide a concise summary and explanation of herbal drugs and their role in improving neuroplasticity. We review the pharmacological activity of polyherbal formulations produced from some of the most frequently referenced botanicals for the treatment of cerebral ischemia damage. A systematic literature review of bentham, scopus, pubmed, medline, and embase (elsevier) databases was carried out with the help of the keywords like neuroplasticity, herbal drugs, neural progenitor cells, neuroprotection, stem cells. The review was conducted using the above keywords to understand the therapeutic and mechanistic role of herbal neuroprotective agents on neuroplasticity in cerebral ischemic-reperfusion injury. Neuroplasticity emerged as an alternative to improve recovery and management after cerebral ischemic reperfusion injury. Neuroplasticity is a physiological process throughout one's life in response to any stimuli and environment. Traditional herbal medicines have been established as an adjuvant to stroke therapy since they were used from ancient times and provided promising effects as an adjuvant to experimental stroke. The plants and phytochemicals such as Curcuma longa L. , Moringa oliefera Lam , Panax ginseng C.A. Mey., and Rehmannia glutinosa (Gaertn.) DC., etc., have shown promising effects in improving neuroplasticity after experimental stroke. Such effects occur by modulation of various molecular signalling pathways, including PI3K/Akt, BDNF/CREB, JAK/STAT, HIF-1α/VEGF, etc. Here, we gave a perspective on plant species that have shown neuroprotective effects and can show promising results in promoting neuroplasticity with specific targets after cerebral ischemic reperfusion injury. In this review, we provide the complete detail of studies conducted on the role of herbal drugs in improving neuroplasticity and the signaling pathway involved in the recovery and management of experimental stroke. [Display omitted] • Neuroplasticity is a process which enables brain to adapt according to environment and stimuli. • Various downstream pathways in cerebral ischemic reperfusion injury directly modulates neuroplasticity. • Many herbal drugs showed neuroprotective effect by altering neuroplasticity. • Polyherbal formulations can also be a intriguing future directions in the treatment of cerebral ischemia. [ABSTRACT FROM AUTHOR]

Tenuigenin (TEN) is a main pharmacologically active component of Polygala tenuifolia Willd. (Polygalaceae), which has shown neuroprotective functions in Alzheimer's disease. Moreover, TEN also demonstrated an anti-oxidative impact in an in vitro model of Parkinson's disease, reducing damage and loss of dopaminergic neurons. This work focuses on the impact of TEN on locomotor recovery following spinal cord injury (SCI) and underpinning molecules involved. A rat model of SCI was generated, and the rats were treated with TEN, oe-PTPN1 (PTP non-receptor type 1), a protein kinase B (Akt)/mammalian target of rapamycin (mTOR) antagonist LY294002, or an autophagy inhibitor 3-methyladenine (3-MA). Subsequently, locomotor function was detected. Pathological changes and neuronal activity in the spinal cord tissues were analyzed by hematoxylin and eosin staining, Nissl staining, and TUNEL assays. Protein expression of Beclin-1 and microtubule associated protein 1 light chain 3 beta (LC3B)-II/LC3B–I, PTPN1, IRS1, mTOR, and phosphorylated Akt (p-Akt) was analyzed by western blot assays. The LC3B expression was further examined by immunofluorescence staining. Treatment with TEN restored the locomotor function of SCI rats, reduced the cavity area and cell apoptosis, upregulated growth-associated protein 43 and neurofilament 200, and decreased the Beclin-1 and LC3B-II/LC3B–I levels in the spinal cord. TEN suppressed PTPN1 protein level, while PTPN1 suppressed IRS1 protein to reduce the p-Akt and mTOR levels. Either PTPN1 overexpression or LY294002 treatment blocked the promoting effect of TEN on SCI recovery. However, treatment with 3-MA suppressed autophagy, which consequently rescued the locomotor function and reduced neuron loss induced by PTPN1. This study demonstrates that TEN suppresses autophagy to promote function recovery in SCI rats by blocking PTPN1 and rescuing the IRS1/Akt/mTOR signaling. [Display omitted] • TEN alleviates neuronal autophagy and restores the locomotor functions of SCI rats. • TEN suppresses PTPN1 to activate the IRS1/Akt/mTOR signaling pathway. • Overexpression of PTPN1 blocks the treating effect of TEN on SCI. • Specific inhibition of the Akt/mTOR signaling blocks the treating effect of TEN on SCI. • Artificial inhibition of autophagy promotes functional recovery in SCI rats. [ABSTRACT FROM AUTHOR]

Pulmonary fibrosis (PF) is a persistent and refractory illness accompanied by inflammation and fibrosis. Gracillin, a natural steroidal saponin, is one of the components of Dioscorea quinqueloba which has been used in herbal medicines for treating some inflammatory diseases. Therefore, it may be a potential drug candidate for PF management. This study aims to elucidate and verify the anti-pulmonary fibrosis effect of gracillin. We established an in vivo model of PF by treatment of mice with bleomycin (BLM) and an in vitro model by treatment of NIH-3T3 cells with TGF-β1. Pathological changes to the structure of lung tissue, pulmonary function, inflammatory exudation of bronchoalveolar lavage fluid (BALF) and deposition of collagen were detected in vivo , and extracellular matrix (ECM) deposition and migration were evaluated in vitro. The significance of gracillin on STAT3 phosphorylation and nuclear translocation were evaluated by western blotting, immunohistochemistry and immunofluorescence assays. The STAT3 transcriptional activity was quantified with a dual-luciferase reporter assay. Recovery experiments were performed by plasmid-directed overexpression of STAT3. We found that gracillin could improve pulmonary function, reduce lung inflammation and mitigate collagen deposition to ameliorate BLM-induced PF in mice. Gracillin also suppressed TGF-β1-induced increases in ECM deposition biomarkers, including COL1A1, fibronectin, α-SMA, N-cad and vimentin, and repressed migration in NIH-3T3 cells. Additionally, gracillin suppressed the phosphorylation, nuclear translocation and transcriptional action of STAT3. Furthermore, the decreased ECM deposition and migration upon gracillin treatment were abrogated upon overexpression of STAT3 in NIH-3T3 cells. Gracillin protects against PF by inhibiting the STAT3 axis, providing a safe and efficacious approach to treating PF. Schematic diagram summarizing the mechanism by which gracillin suppresses pulmonary fibrosis via inhibiting the STAT3 signaling pathway. [Display omitted] • Gracillin alleviates BLM-induced pulmonary fibrosis in mice. • Gracillin reduces TGF-β1-induced extracellular matrix deposition, fibroblast-to-myofibroblast transition and cell migration. • Inhibition of STAT3 signaling pathway may be an important mechanism by which gracillin ameliorates pulmonary fibrosis. [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Sijunzi decoction is a well-known traditional Chinese medicine (TCM) commonly used for invigorating vital energy and for the enhancement of immunity. Modified Sijunzi decoctions have been extensively used to treat cachexia and improve the quality of life of cancer patients undergoing chemotherapy. Aim of the study This study was aimed to provide comprehensive evidence for the anti-cachectic effect of a modified Sijunzi decoction (Zhen-Qi; ZQ-SJZ) and characterize its anti-cachectic mechanism, especially in cisplatin-induced muscle atrophy. Materials and methods We employed a Lewis lung carcinoma (LLC)-induced cancer cachectic mouse model to demonstrate the anti-cachectic effect of ZQ-SJZ. Moreover, we provided an in vitro C2C12 myotube formation model to investigate the effect of ZQ-SJZ in hampering cisplatin-induced muscle atrophy. Results The administration of ZQ-SJZ can recover tumor- and/or cisplatin-induced body weight loss, intestinal mucosal damage, as well as forelimb grip strength and myofiber size. The administration of ZQ-SJZ also significantly prolonged the survival of LLC-induced cachectic mice under cisplatin treatment. Mechanistically, ZQ-SJZ increased the levels of myogenic proteins, such as myosin heavy chain (MyHC) and myogenin, and decreased the atrophy-related protein, atrogin-1, in cisplatin-treated C2C12 myotubes in vitro. In addition, cisplatin-induced mitochondria dysfunction could be hampered by the co-administration of ZQ-SJZ, by which it recovered the cisplatin-mediated decrease in PGC-1α and PKM1 levels. Conclusions The administration of ZQ-SJZ can recover tumor- and/or cisplatin-induced cachectic conditions and significantly prolong the survival of LLC-induced cachectic mice under cisplatin treatment. The profound effect of ZQ-SJZ in hampering tumor- and/or cisplatin-induced cachexia may be due to its modulation of the mitochondrial function and subsequent myogenesis. Taken together, these results demonstrated the anti-cachectic mechanism of ZQ-SJZ and its potential use as a palliative strategy to improve the efficacy of chemotherapy. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Buyang huanwu decoction (BYHWD) is a classic recipe in traditional Chinese medicine (TCM) to supplement Qi and activate blood. It has been used to recover the neural function after the injury of central nervous system for hundreds of years in China. Aim of the study This study investigated whether Buyang huanwu decoction (BYHWD) combined with bone marrow mesenchymal stem cells (BMSCs) transplantation had synergistic effect on neuroprotection of red nucleus neurons after spinal cord injury (SCI). Materials and methods Rubrospinal tract (RST) transection model was established and BMSCs were collected. The forelimb locomotor function was recorded using inclined plate test and spontaneous vertical exploration. cAMP level in red nucleus was detected with Enzyme-linked immunosorbent assay (ELISA). Morphology and number of red nucleus neurons was observed using Nissl's staining. Expression of cAMP-response element binding protein (CREB), ras homolog gene family member A (RhoA) and nerve growth factor (NGF) in red nucleus was detected using immunohistochemistry, qRT-PCR and Western-blotting. Results The combination of BYHWD and BMSCs transplantation could improve the forelimb locomotor function significantly and give the red nucleus somas a better protection. Meanwhile, cAMP level, CREB and NGF increased, while RhoA decreased remarkably in the BYHWD+BMSCs group. Conclusions BYHWD combined with BMSCs transplantation had synergistic effect on neuroprotection of red nucleus neurons after SCI; the mechanism may be related to up-regulating cAMP level, activating the cAMP/CREB/RhoA signaling pathway, and promoting expression of NGF. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Abstract Ethnopharmacological relevance Naoxintong (NXT) is a compound preparation that is widely used in patients with cardiovascular and cerebrovascular diseases. Aim of study The aim of this study is to investigate the protective mechanism of NXT on the mice model of peripheral vascular disease (PAD). Materials and methods In the study, hindlimb ischemia was induced by ligation of femoral artery on the right leg of mice. After surgery, the mice were administrated with saline solution, 10 mg/kg/d simvastatin and 700 mg/kg/d NXT for 4 weeks. The blood flow perfusion was measured by laser Doppler perfusion imaging system. Histological and immunofluorescent staining was used to determine muscle recovery, capillary density, tissue vascular endothelial growth factor (VEGF), phosphorylated-Akt (p-Akt) and phosphorylated-endothelial nitric oxide synthase (p-eNOS) expression. Terminal deoxynucleotidyl transferased UTP nick end labeling (TUNEL) was performed to detect the apoptosis of myocytes in hindlimb. The autophagy-associated gene expression and peroxisome proliferator-activated receptors (PPARs) expression were measured by Quantitative Real-Time Reverse Transcription Polymerase Chain Reaction (qRT-PCR). Western blotting was performed to detect the expressions of light-chain 3 (LC3), VEGF, p-Akt, p-eNOS and PPARs. The EMSA experiment was performed to figure out whether PPARδ could directly bind to the predicted PPRE motif of VEGF. Results NXT treatment significantly accelerated perfusion recovery and reduced tissue injury in mice muscle. Apoptosis and autophagy were decreased within the ischemic muscle of NXT-treated mice. Quantification of vessels in hindlimb muscles provided evidences that NXT promoted angiogenesis in peripheral ischemia. In addition, results from western blotting and immunofluorescent staining suggested NXT induced angiogenesis via VEGF/Akt/eNOS signaling pathway. More interestingly, NXT specifically increased the expression of PPARδ in both mRNA and protein levels. EMSA results showed that PPARδ associated with PPRE site of VEGF promoter, suggesting that NXT-induced VEGF expression is mediated, at least in part, by PPARδ. Conclusion In conclusion, the present study implicated that the restoration of hindlimb blood perfusion and recovery of limb functions were improved in NXT-treated mice with significant improvement of angiogenesis mediated by PPARδ-VEGF-Akt-eNOS axis as well as attenuation of autophagy and apoptosis. These results expand knowledge about the beneficial effects of NXT in angiogenesis and blood flow recovery. It might provide insight into the PPARδ regulating neovascularization in hindlimb ischemia and identify NXT as a potent new compound used for the treatment of peripheral vascular disease. Graphical abstract fx1 [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Ficus carica fruit, a source of bioactive functional ingredients, have been traditionally long time used for its medicinal benefits as they improve the digestive system, treating constipation and used as a natural laxative. Aim of the study The recent study was investigated the ameliorative effect of Ficus carica L. aqueous extract (FCAE) on delayed gastric emptying and ulcerative colitis-improved motility disturbances in dextran sulfate sodium (DSS)-induced acute colitis in rats. Materials and methods Wistar rats were assigned randomly and received 5% DSS for seven days. Ulcerative colitis diagnosis was confirmed by clinical signs, visible fecal blood and histopatological evaluation. The estimation of the action of colitis on TGI and constipation as well as the protective effect of extract, the intestinal biochemical and physiological parameters were measured using the charcoal meal test, loperamide (Lop)-induced constipation as well as spectrophotometric assays. FCAE (150 and 300 mg kg −1 ) was administered orally once per day for seven days 1 h after the loperamide treatment. Phenol-red colorimetric method was used to explore the action of FCAE on gastric emptying process. Results Ulcerative colitis caused a significantly gastrointestinal motility inhibition in normal rats and notably aggravated the constipation in LOP group. Oppositely, FCAE oral intake significantly increased levels of the gastrointestinal transit ratio and gastric emptying by accelerating of their times. Moreover, constipation severity induced by colitis was remarkably reduced in the FCAE treatment group, as demonstrated by a marked management of fecal parameters, water content, oxidative stress indicators, lipid metabolism, and intracellular mediators. Phytochemical analysis of FCAE revealed the presence of carbohydrates, polysaccharides, phenolic acids as gallic acid, chlorogenic acid, syringic acid and ellagic acid, and flavonoids ( e.g. rutin, catechin, epicatechin and apeginine). Conclusions The obtained results indicated that FCAE exhibits a natural laxative effect without provoking diarrhea and ameliorates functional gastrointestinal (GI) and motility disorders thus justifying its traditional usage. [ABSTRACT FROM AUTHOR]

The Chinese traditional medicine frankincense, which can promote blood circulation, is often used to treat skin lesions, including frostbite. To explore the properties of frankincense oil extract (FOE) and its active ingredients and their effect on frostbite wound recovery as an approach to understand the mechanism associated with microcirculation-improvement therapy. The microcirculation-improving effects of FOE and its active ingredients were evaluated using liquid nitrogen-induced frostbite animal models. The rewarming capacity of FOE on the skin was determined through infrared detection, and frostbite wound healing was evaluated following haematoxylin and eosin (H&E) staining and fibre analysis. Moreover, related factors were examined to determine the anti-apoptotic, anti-inflammatory, and microcirculatory properties of FOE and its active ingredients on affected tissue in the context of frostbite. FOE and its active ingredients rapidly rewarmed wound tissue after frostbite by increasing the temperature. Moreover, these treatments improved wound healing and restored skin structure through collagen and elastin fibre remodelling. In addition, they exerted anti-apoptotic effects by decreasing the number of apoptotic cells, reducing caspase-3 expression, and eliciting anti-inflammatory effects by decreasing COX-2 and β-catenin expression. They also improved microcirculatory disorders by decreasing HIF-1α expression and increasing CD31 expression. FOE and its active components can effectively treat frostbite by enhancing microcirculation, inhibiting the infiltration of inflammatory cells, decreasing cell apoptosis, and exerting antinociceptive effects. These findings highlight FOE as a new treatment option for frostbite, providing patients with an effective therapeutic strategy. [Display omitted] • FOE and three ingredients can treat frostbite by enhancing microcirculation. • FOE and three ingredients have anti-inflammatory and anti-apoptotic effects. • FOE and three ingredients can rapidly rewarm and enhance wound healing of frostbite. • FOE and three ingredients enhance collagen and elastin fibre remodelling of frostbite. [ABSTRACT FROM AUTHOR]

Ji-Ming-Shan (JMS) is a traditional herbal prescription consisting of seven herbs including Areca cathechu Burm.f. , Citrus reticulata Blanco , Chaenomeles speciosa (Sweet) Nakai , Euodia ruticarpa (A. Juss.) Benth. , Perilla frutescens (L.) Britton , Zingiber officinale Roscoe, Platycodon grandiflorus (Jacq.). It was first recorded during the Song dynasty and has been used extensively for protection against rheumatism, treatment of swelling of tendons, relief from foot pain, gout and diuresis and other forms of inflammation. The aim of this study is to evaluate the anti-inflammatory and anti-osteoarthritis activity of JMS extracts with the use of different cell lines (RAW 264.7 cells, SW1353 cells and primary cultured rat chondrocytes). MIA-induced rat animal models were used to assess the anti-osteoarthritis activity of the extract. This study investigated the anti-inflammatory activity of JMS-95E on LPS-induced RAW 264.7 macrophages and IL-1β-stimulated chondrocytes. For the in vivo study, male Wistar rats were used and they were randomly assigned in different groups: blank, control, positive control and three different JMS-95E treatment groups (200, 400, 800 mg/kg/d). Paw edema, hind-limb weight bearing, serum inflammatory cytokines including hematoxylin and eosin (HE) staining experiments were used to assess the efficacy of the extract in the rat model. JMS 95% ethanol extract (JMS-95E, marker substance: narirutin (5.10 mg/g) and hesperidin (11.33 mg/g) has been identified in the extract using high pressure liquid chromatography. For in vitro assays, JMS-95E did not exhibit cytotoxicity and was able to downregulate the protein expression of iNOS, COX-2 and MMP-13. The production of inflammatory mediators such as NO and PGE 2 were also reduced with an increase in dose-dependent manner in various cell lines. Inhibitory activity on the key enzyme xanthine oxidase was also observed in this study. In rat animal models, JMS-95E reduced the inflammatory responses such as acute swelling, chondrocyte degradation and pain section of paw edema in rat model. Molecular marker studies of inflammation demonstrated that JMS-95E significantly decrease PGE 2 expression in MIA model. JMS-95E inhibited the inflammatory pathway leading to the production or expression levels of NO, iNOS, COX-2 and PGE 2 in macrophage cells. In primary cultured rat chondrocytes iNOS and SW1353 MMP-13 expression were downregulated after JMS-95E treatment. For the in vivo study JMS-95E significantly reduced the paw volume of carrageenan-induced rat paw edema through each dose and significantly inhibited paw volume, counterweight the distribution of hind-paw weight bearing through the MIA model which means JMS-95E could promote recovery of the acute swelling and chondrocyte degradation of the ankle joints. The above results provided the multiple mechanism of JMS-95E in OA treatment of the scientific founding which supported the description of JMS in traditional use. [Display omitted] [ABSTRACT FROM AUTHOR]

Severe Acute Respiratory Syndrome (SARS) due to the novel coronavirus has become the highest priority that threatens human health. This situation demands widespread vaccination and the innovation of new therapeutic methods. Despite drug discoveries, the need for approving new medicaments is felt because of adverse effects and lack of efficacy. Several medicinal plants including Viola odorata L. are recommended in traditional Persian medicine for alleviating respiratory infection symptoms. Recent studies showed anti-inflammatory, antioxidant, anti-asthmatic, antitussive, analgesic, and antibacterial activities of sweet violet. These enhance respiratory functions, reduce pulmonary inflammation, and decline mucous membrane edema. This study aimed to evaluate the efficacy of sweet violet syrup in alleviating the manifestations of COVID-19 infection. A randomized parallel-group double-blind controlled trial was conducted at Al-Zahra general hospital, Isfahan, Iran. A total of 108 outpatients were enrolled in the study. The patients were randomly allocated to intervention and placebo groups, with 54 patients in each group. The allocation was concealed using sealed opaque envelopes. The intervention group received violet syrup and the control group received placebo syrup, an add-on to the conventional treatment. The outcomes were COVID-19 manifestations, such as dyspnea, cough, myalgia, headache, and diarrhea, considered as outcomes of the study and were evaluated twice using a visual analog scale before the intervention and after 7 days, at the end of the study. Patients were followed daily by phone calls to monitor proper drug consumption and possible side effects. No significant difference was between groups regarding demographic characteristics and vital signs before and after the treatment. Although all symptoms have improved significantly in both groups, patients who received violet syrup recovered faster and the mean severity scores of cough (P = 0.025), myalgia (P = 0.036), headache (P = 0.037), and diarrhea (P = 0.044) decreased greater in comparison to control group. This study, the first clinical trial on the effectiveness of Viola odorata on SARS-CoV-2 patients, showed that Viola odorata L. effectively controls prevalent manifestations of COVID-19 including cough, myalgia, headache, and diarrhea. Regarding this survey, the violet syrup can be mentioned as a complementary treatment for viral influenza-like infections in which cough, myalgia, headache, and diarrhea are prominent. [Display omitted] • Viola odorata is recommended in Persian medicine for respiratory infection symptoms. • This study showed that Viola odorata L. is effective in the treatment of COVID-19. • The drug could relieve cough, myalgia, headache, and diarrhea in SARS-CoV-2 patients. • Violet syrup had no side effects in COVID patients. • It seems the drug subsides lung inflammation and reduces the disease progression. [ABSTRACT FROM AUTHOR]

Ethnopharmacological studies for drug discovery from natural compounds play an important role for developing current therapeutical platforms. Plants are a group of natural sources which have been served as the basis in the treatment of many diseases for centuries. In this regard, Ceratonia siliqua (carob) is one of the herbal medicine which is traditionally used for male infertility treatments. But so far the main mechanisms for effects of carob are unknown. Here, we intend to investigate the ability of carob extract to induce spermatogenesis in an azoospermia mouse model and determine the mechanisms that underlie its function. This is a pre-clinical animal model study to evaluate the effect of carob extract in spermatogenesis recovery. We established an infertile mouse model with the intent to examine the ability of carob extract as a potential herbal medicine for restoration of male fertility. Sperm parameters, as well as gene expression dynamics and levels of spermatogenesis hormones, were evaluated 35 days after carob administration. Significant enhanced sperm parameters (P < 0.05) showed that the carob extract could induce spermatogenesis in the infertile mouse model. Our data suggested an anti-apototic and inducer role in the expressions of cell cycle regulating genes. Carob extract improved the spermatogenesis niche by considerable affecting Sertoli and Leydig cells (P < 0.05). The carob-treated mice were fertile and contributed to healthy offspring that matured. Our data confirmed that this extract triggered the hormonal system, the spermatogenesis-related gene expression network, and signaling pathways to induce and promote sperm production with notable level (P < 0.05). We found that the aqueous extract consisted of a polar and mainly well water-soluble substance. Carob extract might upregulate spermatogenesis hormones via its amino acid components, which were detected in the extract by liquid chromatography-mass spectrometry (LC-MS). Our results strongly suggest that carob extract might be a promising future treatment option for male infertility. This finding could pave the way for clinical trials in infertile men. This is the first study that has provided reliable, strong pre-clinical evidence for carob extract as an effective candidate for fertility recovery in cancer-related azoospermia. [Display omitted] [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Preparation of Laggera aurita Linn. (Asteraceae) is widely used in traditional medicine to treat various kinds of diseases such as epilepsy, malaria, fever, pain and asthma. Its efficacy is widely acclaimed among communities in Northern Nigeria. Aim of the study The present study is aimed at establishing the possible anticonvulsant effects of the methanol leaf extract of Laggera aurita using acute and chronic anticonvulsant models. Materials and method Median lethal dose (LD 50 ) was determined in mice and rats via oral and intraperitoneal routes. Anticonvulsant screening of the extract was performed using maximal electroshock-induced seizure test in day-old chicks; pentylenetetrazole-, strychnine- and picrotoxin- induced seizure models in mice. Similarly; its effects on pentylenetetrazole-induce kindling in rats as well as when co-administered with fluphenamic and cyproheptadine in mice, were evaluated. Results Median lethal dose (LD 50 ) values were found to be >5000 mg/kg, p.o. and 2154 mg/kg, i.p. , each for both rats and mice. The extract showed dose dependent protection against tonic hind limb extension (THLE) and significantly (p<0.05) decreased the mean recovery from seizure in the maximal electroshock-induced seizure. In the pentylenetetrazole-induced seizure model, the extract offered 50% protection at 600 mg/kg and also increased the mean onset of seizure at all doses with significant (p<0.05) increase at the highest dose (600 mg/kg). Similarly the extract produced significant (p<0.05) increase in the onset of seizures in both strychnine- and picrotoxin- induced seizure models, at all the doses except at 150 mg/kg for the picrotoxin model. Co-administration of fluphenamic acid (FFA) (5 mg/kg) and the extract (600 mg/kg) showed an enhanced effect with percentage protection of 70% while co-administration of FFA (5 mg/kg) and phenytoin (5 mg/kg) as well phenytoin (5 mg/kg) and the extract (600 mg/kg) produced an additive effect. Administration of the extract (600 mg/kg), phenytoin (20 mg/kg) and cyproheptadine (4 mg/kg) offered 40%, 100% and 0% protection against THLE, each respectively, while co-administration of cyproheptadine (4 mg/kg) and the extract (600 mg/kg) as well as co-administration of cyproheptadine (4 mg/kg) and phenytoin (20 mg/kg) offered reduced protection of 20% and 50% each respectively. The extract at all doses reduced the severity of seizure episodes induced by PTZ-induced kindling. Conclusion The results suggest that the methanol leaf extract of Laggera aurita possesses anticonvulsant and antiepileptogenic properties. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Wei-Chang-An pill (WCA pill), a traditional Chinese pharmaceutical preparation, possessed potential anti-inflammatory advantages and noteworthy gastrointestinal regulations in digestive diseases, which might represent a promising candidate for the treatment of intestinal mucositis (IM) induced by 5-fluorouracil (5-FU). Aim of the study To analyze the bioactive constituents and investigate the effect of methanol extraction from WCA pill (WCA ext) on 5-FU induced IM with underlying mechanisms. Materials and methods The analysis of serum bioactive constituents after WCA ext administration in rats was carried out by UHPLC-Quadrupole-Time of Flight-Mass Spectrometry. In mice, IM was induced by 5-FU and physical manifestations were measured during the period of drug delivery. Half of mice were assessed with histology, expression of inflammatory cytokines in ileum and plasma via hematoxylin and eosin staining, immunohistochemical staining as well as cytokine enzyme-linked immunosorbent assay test, respectively. Besides, gastric emptying (GE) and gastrointestinal transit (GIT) were further tested in the other half of 5-FU induced mice. Results Twenty-two compounds were identified or tentatively characterized. IM induced by 5-FU was improved significantly after treatment with WCA ext through reducing the body weight loss, relieving the severe diarrhea, and inhibiting the GE as well as GIT. Further assessments validated that WCA ext promoted the recovery of intestinal mucosa, evaluated the activity of enterocyte proliferation, maintained the integrity of tight junction, and ameliorated the inflammatory disturbances. Conclusions These results suggested that WCA ext promoted the restoration of intestinal function in 5-FU-induced IM via regulating multiple sites of actions in intestinal homeostasis. Accordingly, WCA pill might be a promising therapeutic candidate for the prevention of IM during cancer chemotherapy. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Acupuncture is a key part of traditional Chinese medicine, shown to induce favorable neuroplasticity for injuries in the central and peripheral nervous systems. Recent studies report elongated needle therapy (ENT) with BL54 and ST28 may restore acute spinal cord injury (ASCI). However, the precise mechanism for this has not been elucidated. Aim of the study In our current study, we investigated the effects of ENT on inflammation and neuronal apoptosis induced by ASCI, and whether PI3K/Akt and MAPK/ERK signaling pathways are involved in the ENT restoration effect. Materials and methods Rat models of moderate SCI were established in accordance with the modified Allen's method and were treated with ENT continuously for 7 days. Spontaneous activities were evaluated by the Basso Beattie and Bresnahan locomotor scale. Levels of inflammatory cytokines, such as tumor necrosis factor alpha, interleukin-6, IL-1β, and nuclear factor kappa-β, were determined by enzyme-linked immunosorbent assay. Cell apoptosis was examined by the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The proportions of cells with positive Bcl-2 and Bax expression were determined by immunohistochemical assays, whilst the expression profiles of p-AKT and p-ERK in spinal cord tissues were evaluated by western blotting. Furthermore, the expression profiles of Cytochrome-C (Cyt-C) and caspase-3 in vivo were analyzed by reverse transcription polymerase chain reaction. The potential inhibitory effects downstream of the Akt and ERK signaling pathways were examined by administration of specific inhibitors LY294002 and PD98059 in vivo. Results As indicated by this study, inflammation as well as PI3K/Akt- and MAPK/ERK signaling pathway-mediated neuronal apoptosis were involved in the course of SCI in rats. The neuro-protective effect of ENT was associated with reduced Bax protein-positive neurons and increased Bcl-2 protein-positive neurons. ENT enhanced recovery of rat activities. Activation of p-Akt and p-ERK in the PI3K/Akt and MAPK/ERK signaling pathways, inhibited expression of the critical component Cyt-C. Cyt-C is required for the mitochondrial apoptosis pathway and cascade of caspase-3, which is involved in activation of neuronal apoptosis through down-regulation of Bax protein and up-regulation of Bcl-2, as determined by TUNEL. The administration of PI3K/Akt and MAPK/ERK signaling pathway specific inhibitors, LY294002 and PD98059, suppressed expression of both p-Akt and p-ERK. Conclusion ENT with BL54 and ST28 points can promote the recovery of ASCI. And the neuro-protective effect of ENT during the restoration of SCI may be associated with the suppression of both inflammation and activation of PI3K/Akt and MAPK/ERK signaling pathways, resulting from down-regulation of Bax protein, up-regulation of Bcl-2, and inhibition of the mitochondrial apoptosis pathway. [ABSTRACT FROM AUTHOR]

Helminthostachys zeylanica (HZ), which is also called "Dao-Di-U-Gon" in Taiwan, has anti-inflammatory and antiedema effects and is commonly used to treat edema in patients with fractures. The ugonin K component of HZ can induce osteogenesis and promote bone mineralization, its therapeutic effect, however, its therapeutic effect remains unclear. Therefore, the purpose of the present study was to investigate the effect of HZ on functional recovery in patients with ankle fractures requiring surgical treatment. A double-blinded, randomized, controlled study was conducted. A total of 45 patients with ankle fractures requiring surgical treatment were assigned to either the control group (n = 23 patients), which received the oral administration of HZ placebo 1.0 g t.i.d. for 42 days continuously, or to the treatment group (22 patients), which received HZ for 42 days. The serum amino-terminal propeptide of type 1 procollagen (PINP) levels were similar in the first assessment (V1) between the control (45.90 ± 16.31 ng/mL) and treatment groups (52.61 ± 21.02 ng/mL; p = 0.240); the differences in PINP level between the third assessment (V3) and V1 were greater in the treatment group (35.84 ± 24.56 ng/mL) than in the control group (16.34 ± 11.97 ng/mL; p = 0.002). Radiographic healing time (RHT) was 9.09 ± 1.15 weeks in the treatment group, which was shorter than the 9.91 ± 0.79 weeks (p = 0.012) in the control group. Oral administration of HZ for 42 days can increase serum PINP level and reduce the RHT. Therefore, HZ can be used to treat patients with ankle fractures requiring surgical treatment. However, a larger sample size is needed in future studies. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Ethnopharmacological relevance: Salvia miltiorrhiza, a well-known traditional Chinese medicine, is commonly used to treat some neurological diseases because of its anti-oxidative, anti-inflammatory and anti-apoptotic properties. We investigate whether Salvia miltiorrhiza can improve the differentiation of induced pluripotent stem cells (iPSCs) into neurons in vitro, and promote iPSCs-derived neural stem cells survival, integrate, and differentiation after their transplantation to the ischemic brain tissues. Materials and methods: Induced pluripotent stem cells were used to differentiate into neural stem cells, and further into neurons in induction medium with various concentrations of Salvia miltiorrhiza. The effects were assessed by immunofluorescence staining, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. iPSC-derived neural stem cells were transplanted into the brains of rats with middle cerebral artery occlusion, immunofluorescence staining was used to evaluate survival, integrate, and differentiation of grafted cells, the functional recovery of the animals was tested by the Longa scores and spontaneous motor activity. Results: Salvia miltiorrhiza (5μg/ml) significantly increased the gene and protein expression of Nestin compared with that in other groups. Microtubule-associated protein 2 (MAP2) expression in induction medium with 5μg/ml Salvia miltiorrhiza was significantly higher than that in the control group. After cells transplantation into the ischemic brain, more grafted MAP2+ cells were found in Salvia miltiorrhiza-treated rats than others at 7 days. Salvia miltiorrhiza-treated rats showed the most remarkable functional recovery at 7 and 14 days. Conclusion: Salvia miltiorrhiza induces differentiation of induced pluripotent stem cells to differentiate into neurons efficiently. The plant provides neuroprotection to implanted cells and improves functional recovery after their transplantation to the ischemic brain tissues. [Copyright &y& Elsevier]

As of September 17, 2021, coronavirus disease 2019 (COVID-19) has infected more than 226 million people in a worldwide pandemic, with conservative estimates suggesting that there are more than 204 million convalescent patients with COVID-19. Previous studies have indicated that patients in the recovery phase exhibit decreased function of multiple organs. In China, traditional Chinese medicine (TCM) treatment is recommended in the rehabilitation period of COVID-19; however, the safety and efficacy of such treatment remain to be confirmed. The present study aimed to evaluate the efficacy and safety of Bufei Huoxue (BFHX) in restoring the functional status and exercise tolerance of patients recovering from COVID-19. A total of 131 patients in the rehabilitation period of COVID-19 infection were randomly divided into a Bufei Huoxue (BFHX) group (n = 66) and a placebo group (n = 65). BFHX or placebo was given orally three times a day (1.4 g/dose) for 90 days. The primary outcomes was to evaluate improvements in exercise tolerance and imaging manifestations on chest computed tomography (CT). After the exclusion of two patients who withdrew prior to receiving any medications, 129 patients were recruited, including 64 patients in the BFHX group and 65 patients in the placebo group. After 3 months of treatment, the BFHX group exhibited greater attenuation of pneumonia lesions on chest CT than the placebo group (P < 0.05). Improvements in 6-min walk distance (6MWD) relative to baseline were also significantly better in the BFHX group than in the placebo group (P < 0.01). Scores on the Fatigue Assessment Inventory (FAI) were lower in the BFHX group than in the placebo group (P < 0.05). Although the rate of adverse events was higher in the BFHX group than in the placebo group (9.38% vs. 4.62%), the difference was not significant (P = 0.3241). BFHX may exert strong rehabilitative effects on physiological activity in patients recovering from COVID-19, which may in turn attenuate symptoms of fatigue and improve exercise tolerance. [Display omitted] • This prospective study assessed the efficacy and safety of BFHX in treating patients recovering from COVID-19. • BFHX may have strong rehabilitative effects on patients recovering from COVID-19. • BFHX reduces fatigue symptoms and improves exercise tolerance. [ABSTRACT FROM AUTHOR]

Bai-Hu-Tang (BHT) is traditionally used to treat human and animal fever syndrome with four symptoms: large and vigorous pulse, large thirst, high sweat, and high heat. To investigate the mechanism of vasodilation regulation of Bai-Hu-Tang in primary vascular endothelial cells stimulated by lipopolysaccharide (LPS). A hydrophilic concentrate of BHT was prepared, and the main components of mangiferin and timosaponin BⅡ were determined by HLPC analysis. The rabbit fever model was constructed by intravenous injection of LPS (15 μg/kg body weight), and BHT was gavaged to treat febrile rabbits. After treatment for 6 h, animal peripheral blood was collected, and serum was isolated for endothelin-1 (ET-1) and nitric oxide (NO) assays. Rabbit vascular endothelial cells (RVECs) were isolated and stimulated with 1 μg/mL LPS, and then inflammatory cells were treated with 125 or 250 μg/mL BHT for 24 h. The supernatant cytokines TNF-ɑ, IL-1β, IL-6, and ET-1 were detected by ELISA kits. Gene expression levels of endothelin receptor type B (ET B receptor) were analysed by real-time polymerase chain reaction (RT-PCR), and protein expression levels of PI3K and Akt were detected by Western blot. A nitrite assay was used to measure intracellular nitric oxide (NO) production, and nitric oxide synthase (NOS) was measured by the T-NOS colorimetric method. Animal experiments demonstrated that BHT significantly restored ET-1 and NO in animal peripheral blood, which were disordered in LPS-induced fever rabbits. Moreover, a cytotoxicity assay demonstrated that BHT ≤700 μg/mL is innoxious to RVECs. BHT significantly repressed cellular TNF-α, IL-1β, and ET-1, which were originally elevated by LPS in RVECs. Meanwhile, BHT elevated the gene expression level of the ET B receptor and promoted NOS and NO production in RVECs induced by LPS. BHT can inhibit excessive ET-1 secretion induced by LPS in vascular endothelial cells and activate the classic ET-1 signalling pathway to promote NO production, which may facilitate vasodilation of smooth muscle cells. [Display omitted] • Bai-Hu-Tang inhibits LPS inflammatory response in vascualar endothelial cells. • Bai-Hu-Tang inhibits excessive secretion of endthelin-1 induced by LPS in vascualar endothelial cells. • Bai-Hu-Tang activates classical ET-1 signaling pathway to promote NO production in vascualar endothelial cells. [ABSTRACT FROM AUTHOR]

Nigella glandulifera Freyn et Sint. (N. glandulifera) seeds are widely used in traditional Uyghur medicine for a variety of immuno-inflammatory diseases. The total saponins from N. glandulifera seeds (TSNGS) have been shown to have analgesic, antioxidant, and anti-inflammatory effects that can alleviate joint pain and swelling. Rheumatoid arthritis (RA) is a chronic and progressive, debilitating autoimmune disease for which current treatments are not sufficiently effective and result in unsatisfactory side effects. This study aimed to mechanistically investigate the therapeutic effects of TSNGS on RA. Qualitative analysis of TSNGS was performed using ultra-high-performance liquid chromatography-Q-Orbitrap-high-resolution mass spectrometry. Rats with collagen-induced arthritis (CIA), IL-1β-induced HFLS-RAs, and VEGF-induced HUVECs were analyzed to determine the efficacy and mechanism of TSNGS on RA. Twenty-one compounds were identified in TSNGS. TSNGS (10, 50, or 250 mg/kg) reduced the severity of arthritis, indicated by a lower arthritis score, reduced paw swelling, and body weight in rats with CIA. TSNGS ameliorated histopathological changes involving inflammatory infiltration, bone degeneration, and angiogenesis in knee and ankle joints. TSNGS improved the immuno-inflammatory response by restoring the levels of the cytokines IFN-γ, TNF-α, IL-1β, IL-6, IL-17A, IL-4, and IL-10, and increasing the number of CD4+CD25+ Tregs in the peripheral circulation and Foxp3 levels in knee joints in rats with CIA. Furthermore, TSNGS increased the OPG/RANKL ratio and downregulated p-p65 in serum and joint synovia. Inhibition of angiogenesis by TSNGS was associated with recovery of the angiogenesis-related Ang/Tie-2 signaling pathway. It was established that TSNGS provides a therapeutic effect on RA by alleviating synovitis, bone degeneration, and angiogenesis via the OPG/RANKL/NF-κB and Ang/Tie-2 pathways and may be used for the treatment of RA. [Display omitted] • TSNGS may have potential as a novel treatment for RA. • TSNGS decreased the severity of arthritis in rats with CIA. • TSNGS reduced synovitis associated with RA via OPG/RANKL/NF-κB pathway. • TSNGS alleviated angiogenesis related to RA via Ang/Tie-2 signaling. • TSNGS upregulated the level of CD4+CD25+ Tregs and Foxp3 in rats with CIA. [ABSTRACT FROM AUTHOR]

Tibetan ginseng named Wangla (tuber of Coeloglossum viride var. bracteatum) is a traditional tonic that has Yang-strengthening and qi-enhancing, tranquilizing, intelligence-enhancing and longevity-enhancing properties. It has been used to treat impotence, spermatorrhea, anemia and insomnia. Therefore, its characteristic components and neuronal modulating effects were studied. Aim of the study: To investigate the elimination of Aβ-induced toxicity by CE and to elucidate the molecular mechanisms involving BDNF, FGF2, and their related signaling axis, and the RIP1-driven inflammatory pathway. We established Aβ-induced toxicity models in cultured neurons and ICR mice, respectively. MWM and fear conditioning tests were performed for behavioral analysis of cognitive functions in mice. Western blot was used to investigate the levels of BDNF, FGF2, and their downstream effector TrkB/Akt/Bcl-2, as well as the RIP1-driven RIP1/RIP3/MLKL pathway. Immunofluorescence assay is used to examine the status of glial cells. CE abrogated Aβ toxicity and inhibited apoptosis in cultured neurons, mainly by regulating the BDNF, FGF2, and TrkB/Akt signaling pathways as well as RIP1-driven inflammation and necroptosis. Similarly, mice injected intracerebrally with Aβ exhibited cognitive deficits and had elevated oxidative stress and inflammatory factors detected in their serum and brain. However, CE-treated mice showed recovery of cognitive abilities and quelled levels of oxidative stress and inflammatory factors. Moreover, Aβ toxicity led to a reduction in BDNF, FGF2, and related signaling regulators in the hippocampus and prefrontal cortex, accompanied by activation of RIP1-driven inflammatory signaling pathways, and a reduction in TBK1 and Bcl-2. However, CE restored the levels of BDNF, FGF2, and TrkB/Akt signaling pathway, while inhibiting RIP1-induced RIP1/RIP3/MLKL pathway, thereby antagonizing apoptosis and maintaining neuronal activity. CE effectively eliminated the toxicity of Aβ in cultured neurons and mouse models, which holds promise for drug development. Coeloglossum viride var. bracteatum extract (CE) eliminated the toxicity of Aβ, protected neuronal activity and restored cognitive function in mice. [Display omitted] [ABSTRACT FROM AUTHOR]

Abstract: Aim of study: Depression is a psychiatric disorder. Chaihu-Shugan-San (CSS) is a traditional Chinese medicine formula suggested in the treatment of depression, but its effectiveness and safety are not well defined. This meta-analysis aimed to assess the effectiveness and safety of CSS in depression therapy. Materials and methods: The databases including MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, CNKI database, Wanfang Data and VIP Information were searched. Papers were reviewed systematically by two researchers and were analyzed using Cochrane software Revman 5.0. Results: Ten randomized controlled trials comparing 835 subjects were included. Of these studies, seven studies used fluoxetine (20mg, once a day), two used paroxetine (20mg, once a day) and one used doxepin (25mg, two times a day) as the antidepressant drugs. Meta-analyses revealed that CSS in combination with antidepressant drugs treatment significantly improved depressive symptoms (WMD=−3.56; 95% CI −5.09 to −2.03) and significantly increased effective rate (OR=3.31; 95% CI 1.80–6.10) and recovery rate (OR=2.32; 95% CI 1.61–3.34) compared with antidepressant drugs therapy. In addition, the efficacy of CSS as monotherapy was significantly better than antidepressants in improving depressive symptoms (WMD=−3.09; 95% CI −5.13 to −1.06) and in creasing effective rate (OR=2.61; 95% CI 1.23–5.53). CSS was comparable to antidepressants in increasing recovery rate (OR=1.83; 95% CI 0.84–3.98). No serious adverse events were reported in any of the included trials. Conclusion: The present work supported that CSS was effective and safe in treating depressed patients. More full-scale randomized clinical trials with reliable designs are recommended to further evaluate the clinical benefit and long-term effectiveness of CSS for the treatment of depression. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Radix Codonopsis and Radix Astragali, of which Shenqi Fuzheng Injection (SFI) is composed, are commonly used in traditional Chinese medicine to improve immune function against chronic diseases. Aim of the study: The present study was thus designed to systematically elucidate the in vivo immuno-enhancement effects of SFI in immunosuppressed mice induced by cyclophosphamide (Cy) treatment. Materials and methods: Balb/c mice were injected intraperitoneally (i.p.) once daily with low-dose (2.5g raw materials/kg), intermediate-dose (5g raw materials/kg), high-dose (10g raw materials/kg) of SFI for 10 consecutive days, respectively, accompanied by i.p. injection of Cy (80mg/kg) on Days 4–6. Results: Compared with vehicle group, low-, intermediate- and high-dose SFI treatment accelerated recovery dose-dependently of spleen index, peripheral white blood cell and bone marrow cell counts, enhanced T cell and B cell proliferation responses, as well as splenic nature killer cell activity and peritoneal macrophage phagocytosis, and restored the level of interleukin-2 in the serum. Furthermore, SFI treatment promoted recovery of the amount of peripheral white blood cells on Day 6, rather than recombinant human Granulocyte Colony-Stimulating Factor (rhG-CSF) did. Conclusions: These results demonstrate, for the first time, that chronic treatment with SFI results in accelerating recovery of immunosuppression in Cy-treated mice, which is competent in taking into consideration for both precautions and remedy. Our findings provide experimental evidences for further researches and clinical application in cancer patients undergoing chemotherapy. [Copyright &y& Elsevier]

Abstract: Ethnopharmacological relevance: Ginseng, the root of Panax ginseng C.A. Meyer, is one of the most commonly used healing herbs for stroke and chronic debilitating conditions in China. Ginsenosides are the main active principles for ginseng''s efficacy, but the mechanisms have not been fully clarified. Aim of the study: To test the hypothesis whether or not the administration of Ginseng total saponins (GTS) can enhance neurogenesis after focal cerebral ischemia, and thereby improve neurological deficits. Materials and methods: Male Wistar rats received intraperitoneal injections of GTS dissolved at a dose of 25mgkg−1 d−1 or normal saline (NS) of same volume 3 days before the permanent middle cerebral artery occlusion (MCAO) model establishment until the animals were killed at the time points of 1d, 3d, 7d and 14d. The neurological function was assessed blindly. BrdU immunostaining and double staining were performed by following the 3-steps method. Results: (A) GTS-treated rats have better neurological scores compared with those in NS group at 14d time point (p <0.05); (B) the number of BrdU+ cells and BrdU+/NeuN+ cells in GTS group were significantly higher than those in NS group in the ipsilateral subventricular zone and in the ipsilateral infarct area after MCAO, respectively (p <0.05 or p <0.01); (C) the increase of the number of BrdU+/NeuN+ cells highly correlated with the decrease of neurological scores. Coefficient correlation r =−0.828 (p <0.01). Conclusion: GTS can improve neurological deficits after focal cerebral ischemia by inducing endogenous neural stem cells activation and thereby enhance adult central nervous system regeneration. [Copyright &y& Elsevier]

Evidence of phytochemical roles in infant development and maternal recovery offers insights into beneficial functions of traditional plant use during lactation and the postpartum period. Ethnopharmacological research has relevance to global priorities on maternal and child health, to understanding origins and determinants of human self-medication, and for reconciling traditional postpartum practices and mainstream healthcare. Present emerging evidence, within evolutionary and socio-cultural contexts, on the role of maternal consumption on transfer of phytochemicals into breast milk with impacts on maternal and child health, and on infant development. Establish current state of knowledge and an ethnopharmacological research agenda that is attentive to cross-cultural and regional differences in postpartum plant use. An extensive literature review using Medline, Scopus, and Web of Science focused on traditional and contemporary use and socio-cultural context, as well as physiological, pharmacological, toxicological, and behavioral activities of plants used medicinally by women during postpartum recovery and lactation. The most widely reported postpartum plants show antimicrobial, anti-inflammatory, immunological, and neurophysiological activities, with low toxicity. Phytochemicals transfer from maternal consumption into breast milk in physiological concentrations, while animal studies demonstrate immunomodulation and other actions of medicinal plants during lactation. Reporting on the use and diverse traditional knowledge of women about plants during the postpartum period is obscured by the marginal place of obstetric issues and by gender biases in ethnobotanical research. In many contemporary contexts use is prejudiced by precautionary risk warnings in health literature and practice that confound lactation with pregnancy. Although systematic investigation of postpartum plant use is lacking, known pharmacological activities support potential benefits on infant development and maternal health with immediate and long-term consequences in relation to allergic, inflammatory, autoimmune, and other diseases. An ethnopharmacological agenda focused on the perinatal period requires directed methodologies and a regional approach in relation to culturally-specific knowledge and practices, traditional plant use, and local health needs. Testing the hypothesis that phytochemicals transferred from medicinal plants into breast milk impact the human immune system and other aspects of infant development requires extended analysis of phytochemicals in human milk and infant lumen and plasma, as well as effects on gastrointestinal and milk microbiome. [Display omitted] • Integrated socio-cultural, ecological, behavioral, physiological and phytochemical overview. • Perinatal self-medication and a supporting role of women elders key in origins of medicine. • Phytochemicals transferred to breastmilk have potential impacts on immune system and other aspects of neonatal development. • Maternal benefits for physical recovery and disease protection, breastfeeding success, and emotional equilibrium. • Ethnopharmacological research agenda delineated with interconnected traditional botanical knowledge and analytical streams. [ABSTRACT FROM AUTHOR]

Xuesaitong (XST) is a traditional Chinese medicine injection with neuroprotective properties and has been extensively used to treat stroke for many years. The main component of XST is Panax notoginseng saponins (PNS), which is the main extract of the Chinese herbal medicine Panax notoginseng. In this study, we investigated whether XST provided long-term neuroprotection by inhibiting neurite outgrowth inhibitor-A (Nogo-A) and the ROCKII pathway in experimental rats after middle cerebral artery occlusion (MCAO) and in SH-SY5Y cells exposed to oxygen-glucose deprivation/reperfusion (OGD/R). Rats with permanent MCAO were administered XST, Y27632, XST plus Y27632, and nimodipine for 14 and 28 days. Successful MCAO onset was confirmed by 2,3,5-triphenyl tetrazolium chloride (TTC) staining. Neurological deficit score (NDS) was used to assess neurological impairment. Hematoxylin-eosin (HE) staining and immunohistochemical (IHC) analysis of synaptophysin (SYN) and postsynaptic density protein-95 (PSD-95) were performed to evaluate cerebral ischemic injury and the neuroprotective capability of XST. Nogo-A levels and the ROCKII pathway were detected by IHC analysis, western blotting, and quantitative real-time polymerase chain reaction (qRT-PCR) to explore the protective mechanism of XST. OGD/R model was established in SH-SY5Y cells. Cell counting kit 8 (CCK8) was applied to detect the optimum OGD time and XST concentration. The expression levels Nogo-A and ROCKII pathway were determined using western blotting. Our results showed that XST reduced neurological dysfunction and pathological damage, promoted weight gain and synaptic regeneration, reduced Nogo-A mRNA and protein levels, and inhibited the ROCKII pathway in MCAO rats. CCK8 assay displayed that the optimal OGD time and optimal XST concentration were 7 h and 20 μg/mL respectively in SH-SY5Y cells. XST could evidently inhibit OGD/R-induced Nogo-A protein expression and ROCKII pathway activation in SH-SY5Y cells. The present study suggested that XST exerted long-term neuroprotective effects that assisted in stroke recovery, possibly through inhibition of the ROCKII pathway. [Display omitted] [ABSTRACT FROM AUTHOR]

Ashwagandha is a reputed herb in traditional Ayurveda, used for various ailments and improving general well-being. Improved cardiorespiratory endurance can aid in attaining better physiological, metabolic, and functional abilities in humans. According to Ayurveda, Ashwagandha has such potential to improve human health. This study aimed to evaluate the efficacy and safety of Ashwagandha root extract in enhancing cardiorespiratory endurance in healthy athletic adults. Fifty healthy athletic adults were selected randomly and equally allocated to Ashwagandha and placebo groups. The Ashwagandha group received 300 mg of Ashwagandha root extract capsules, twice daily, for 8-weeks. Cardiorespiratory endurance was assessed by measuring the maximum aerobic capacity (VO2 max). Estimation of stress management was done through Total Quality Recovery Scores (TQR), Recovery-Stress Questionnaire for Athletes (RESTQ), and Daily Analysis of Life Demands for Athletes (DALDA) questionnaires along with the antioxidant level measurement. At the end of the study, a statistically significant improvement in VO2 max outcome was observed in the Ashwagandha group when compared to the placebo group (P = 0.0074). The subjects in the Ashwagandha group also displayed a statistically significant increase at the end of the study when compared to the baseline (P < 0.0001). Significantly improved TQR scores were observed in the Ashwagandha group members compared to their placebo counterparts (P < 0.0001). DALDA questionnaire analysis in the Ashwagandha group was found statistically significant (P < 0.0001) compared to the placebo group. RESTQ assessment also yielded better outcomes, especially for fatigue recovery (P < 0.0001), lack of energy (P < 0.0001), and fitness analysis (P < 0.0001). The enhanced antioxidant level was significant (P < 0.0001) in the Ashwagandha group. The present findings suggest that Ashwagandha root extract can successfully enhance cardiorespiratory endurance and improve the quality of life in healthy athletic adults. No adverse events were reported by any of the subjects in this study. [Display omitted] • Ashwagandha is a well-known adaptogen in Ayurveda. • This herb is having great influence in maintaining general well-being in human. • This clinical study suggests that Ashwagandha can boost cardiorespiratory endurance significantly. • Ashwagandha showed improvement in reducing oxidative stress through managing the antioxidant levels. [ABSTRACT FROM AUTHOR]

Cross-cultural comparison of plants used during lactation and the postpartum period offers insight into a largely overlooked area of ethnopharmacological research. Potential roles of phytochemicals in emerging models of interaction among immunity, inflammation, microbiome and nervous system effects on perinatal development have relevance for the life-long health of individuals and of populations in both traditional and contemporary contexts. Delineate and interpret patterns of traditional and contemporary global use of medicinal plants ingested by mothers during the postpartum period relative to phytochemical activity on immune development and gastrointestinal microbiome of breastfed infants, and on maternal health. Published reviews and surveys on galactagogues and postpartum recovery practices plus ethnobotanical studies from around the world were used to identify and rank plants, and ascertain regional use patterns. Scientific literature for 20 most-cited plants based on frequency of publication was assessed for antimicrobial, antioxidant, anti-inflammatory, immunomodulatory, antidepressant, analgesic, galactagogic and safety properties. From compilation of 4418 use reports related to 1948 species, 105 plant taxa were recorded ≥7 times, with the most frequently cited species, Foeniculum vulgare, Trigonella foenum-graecum, Pimpinella anisum, Euphorbia hirta and Asparagus racemosus , 81, 64, 42, 40 and 38 times, respectively. Species and use vary globally, illustrated by the pattern of aromatic plants of culinary importance versus latex-producing plants utilized in North Africa/Middle East and Sub-Saharan Africa with opposing predominance. For 18/20 of the plants a risk/benefit perspective supports assessment that positive immunomodulation and related potential exceed any safety concerns. Published evidence does not support a lactation-enhancing effect for nearly all the most-cited plants while antidepressant data for the majority of plants are predominately limited to animal studies. Within a biocultural context traditional postpartum plant use serves adaptive functions for the mother-infant dyad and contributes phytochemicals absent in most contemporary diets and patterns of ingestion, with potential impacts on allergic, inflammatory and other conditions. Polyphenolics and other phytochemicals are widely immunologically active, present in breast milk and predominately non-toxic. Systematic analysis of phytochemicals in human milk, infant lumen and plasma, and immunomodulatory studies that differentiate maternal ingestion during lactation from pregnancy, are needed. Potential herb-drug interaction and other adverse effects should remain central to obstetric advising, but unless a plant is specifically shown as harmful, considering potential contributions to health of individuals and populations, blanket advisories against postpartum herbal use during lactation appear empirically unwarranted. Image 1 • 4418 global use reports of 1948 species compiled from 331 publications. • Potential role of phytochemicals in immune system and other aspects of neonatal development. • Maternal benefits for involution, postpartum depression, infection, breastfeeding outcomes. • Latex-producing and aromatic plants over-represented with regionally distinct patterns. • Limited empirical evidence of galactogenic activity. [ABSTRACT FROM AUTHOR]

Tubeimoside I (TBM) is a triterpenoid saponin purified from tubeimu (tuber of Bolbostemma paniculatum (Maxim.) Franquet). In traditional Chinese medicine, tubeimu had been used to treat acute mastitis, snake bites, detoxication, inflammatory diseases, and tumors for over 1000 years. This study aimed to investigate whether TBM could promote angiogenesis and how to promote angiogenesis. In vivo , the pro-angiogenic effects of TBM were examined using the hindlimb ischemia model. After the ischemia operation, 1 mg/kg/day TBM was given via intraperitoneal injection for 28 days and the recovery of blood flow was monitored by Doppler scanner every 7 days. The capillary density in gastrocnemius muscle was detected by immunofluorescence. Expression of related proteins were determined by western blotting. In vitro , the pro-angiogenic effects of TBM on HUVECs were examined by Cell Counting Kit-8, scratch assay, endothelial cell tube formation assay and western blotting. TBM improved recovery from hindlimb ischemia in C57BL/6 mice. TBM promoted endothelial cell viability, migration and tube formation in HUVECs. TBM could activate eNOS-VEGF signaling pathway by enhancing expression of eNOS. And TBM's pro-angiogenesis effects could be abolished by L-NAME (an inhibitor of eNOS). TBM promoted angiogenesis via the activation of eNOS-VEGF signaling pathway and TBM could be a novel agent for therapeutic angiogenesis in ischemic diseases. Image 1 [ABSTRACT FROM AUTHOR]

Ginseng (Panax ginseng Meyer) is a well-known herb in traditional Chinese medicine and has been used to treat many diseases for thousands of years. Recent studies have shown that ginseng is a promising agent for improving the gut microbiota and treating ulcerative colitis. Fermentation is a common process in traditional Chinese medicine making that can be used to enhance efficacy and reduce toxicity. The purpose of the present study was to research the efficacy of ginseng fermented with probiotics (Lactobacillus fermentum) on the gut microbiota and immunity of rats with antibiotic-associated diarrhea (AAD). SPF Sprague-Dawley rats were randomly divided into eight groups: control group, antibiotic group, natural recovery group, and five groups treated with different doses of fermented ginseng (FG1 to FG5). A model of AAD was established by treating the rats with triple antibiotics, and obvious symptoms of AAD were observed. A histopathological analysis of the colon was performed. The total bacteria in the intestinal microbiota and five types of gut microbes in the feces were detected by quantitative PCR. The expression levels of related immune factors TLR4 and NF-κB in the colon were assayed. An appropriate dose of fermented ginseng (0.5 g/kg/d) relieved some of the symptoms of AAD and colon inflammation and reduced the expression of the immune factors TLR4 and NF-κB in the colon. The alteration of the gut microbiota observed in the rats treated with antibiotics also returned to normal after treatment with fermented ginseng. Moreover, different doses of fermented ginseng exerted different influences on the gut microbiota, and excessively high or low doses of fermented ginseng were disadvantageous for resolving the symptoms of AAD and promoting recovery. These results demonstrate that fermented ginseng can treat AAD symptoms and colon inflammation and restore the gut microbiota to its original state. Image 1 [ABSTRACT FROM AUTHOR]

Sam So Eum (SSE), used in traditional Korean medicine, has been prescribed for the treatment of various ailments including emesis, and fever for centuries. SSE is known by several different names (Shen Su Yin in traditional Chinese medicine; Jin So In traditional Japanese Kampo medicine). It is a mixture of medicinal plants including Panax ginseng C. A. Mey., Perilla frutescens (L.) Britton, and Peucedanum praeruptorum Dunn. Studies have revealed that SSE has many pharmacological effects including anti-inflammatory, anti-cancer, and anti-allergic properties, but its toxic effects have not been evaluated in vivo. Recently, the use of traditional medicinal herbs to treat various diseases has increased, owing to increased number of studies supporting their efficacy. However, safety evaluations for toxicity and other adverse effects have not been extensive. It is commonly considered that natural products extracted from traditional medicinal herbs are safer than synthetic drugs, but this lacks a scientific basis. Thus, in this study, we evaluated the toxicity of SSE in male and female rats. To evaluated the safety of SSE in male and female rats. SSE was administered orally for 13 weeks at 1000, 2000, and 4000 mg kg−1·day−1, and then the rats were maintained for 4 weeks without SSE administration (recovery evaluation). We observed the animals for changes in clinical signs, including hematological parameters, and food consumption; serum chemistry profiling and urinalysis were also carried out. Creatinine levels in the serum were significantly increased following oral administration of SSE at 2000 and 4000 mg kg−1·day−1 in male and female rats, but returned to the normal levels during the recovery period. In addition, SSE administration does not cause kidney and liver toxicity. Thus, we determined that the no-observed-adverse-effect level of SSE is 4000 mg kg−1·day−1. The no-observed-effect level of SSE was determined to be 1000 mg kg−1·day−1, because serum creatinine was increased by oral administration of SSE at 2000 and 4000 mg kg−1·day−1 in male and female rats. SSE administration does not cause toxicity at 4000 mg kg−1·day−1 in male and female rats. Image 1 [ABSTRACT FROM AUTHOR]

The traditional Mongolian medicine Eerdun Wurile (EW) has remarkable neural recovery effect, and has been playing a key role in the clinical treatment of neurological disorders including ischemic stroke in Inner Mongolia Autonomous Region of China. The preliminary pharmacological studies in animal suggested that EW regulates the expression of trophic factors in brain lesion and may also balance the polarization of activated microglia (Gaowa et al., 2018). Aim of the study : The pool of leading bioactive chemicals underlying the therapeutic effects of EW has not been identified. Therefore, the mechanism of action of EW is poorly understood. This study was aimed to identify the major group of compounds that contribute to the inhibition of neuroinflammation during stroke recovery through regulation of microglia polarization. The extracts of EW in different solvents were evaluated for their inhibitory ability of cytokine (IP-10) expression in LPS stimulated BV2 cells. The most effective extract (of petroleum ether extract) was further separated to 18 fractionations on a semi-preparative HPLC column, which were assess for the IP-10 down-regulation efficiency by RT-qPCR. The potent isolate was further fractionated in 12 fractions, which showed fewer peaks. The fraction 6 from this isolates, which remarkably down-regulates cytokines expression including IP-10, TNFα and IL-1β, was analyzed on UPLC-qTOF MS. The key chemicals were measured for their cytokine inhibition in BV2 cells and mouse primary microglia. After two consecutive fractionating by preparative HPLC, petroleum ether extraction of EW gave 12 fractions with relatively distinctive chromatograms. A particular fraction (fraction 6) preserved the inhibitory effects on expression of pro-inflammatory cytokines including IP-10, TNFα, IL-1β and iNOS. The result of UPLC-qTOF MS analysis showed that the fraction contains 21 chemicals including costunolide, alantolactone, myristicin and linolenic acid, which significantly down-regulate the expression of key pro-inflammatory cytokines in LPS stimulated BV2 cells as well as mouse primary microglia. Collectively our data suggest that the bioactive chemical pool which is responsible for the therapeutic effects of EW can be extracted in petroleum ether, and fractionated to a relatively small multiple components. Such components include known anti-inflammatory chemicals, which may contribute to the possible microglia polarization in brain lesion during the recovery of ischemic stroke. Image 1 [ABSTRACT FROM AUTHOR]