The pathological mechanisms and potential therapeutic drugs for myocardial ischemia reperfusion injury.

BACKGROUND: Cardiovascular disease is the main cause of death and disability, with myocardial ischemia being the predominant type that poses a significant threat to humans. Reperfusion, an essential therapeutic approach, promptly reinstates blood circulation to the ischemic myocardium and stands as the most efficacious clinical method for myocardial preservation. Nevertheless, the restoration of blood flow associated with this process can potentially induce myocardial ischemia-reperfusion injury (MIRI), thereby diminishing the effectiveness of reperfusion and impacting patient prognosis. Therefore, it is of great significance to prevent and treat MIRI. PURPOSE: MIRI is an important factor affecting the prognosis of patients, and there is no specific in-clinic treatment plan. In this review, we have endeavored to summarize its pathological mechanisms and therapeutic drugs to provide more powerful evidence for clinical application. METHODS: A comprehensive literature review was conducted using PubMed, Web of Science, Embase, Medline and Google Scholar with a core focus on the pathological mechanisms and potential therapeutic drugs of MIRI. RESULTS: Accumulated evidence revealed that oxidative stress, calcium overload, mitochondrial dysfunction, energy metabolism disorder, ferroptosis, inflammatory reaction, endoplasmic reticulum stress, pyroptosis and autophagy regulation have been shown to participate in the process, and that the occurrence and development of MIRI are related to plenty of signaling pathways. Currently, a range of chemical drugs, natural products, and traditional Chinese medicine (TCM) preparations have demonstrated the ability to mitigate MIRI by targeting various mechanisms. CONCLUSIONS: At present, most of the research focuses on animal and cell experiments, and the regulatory mechanisms of each signaling pathway are still unclear. The translation of experimental findings into clinical practice remains incomplete, necessitating further exploration through large-scale, multi-center randomized controlled trials. Given the absence of a specific drug for MIRI, the identification of therapeutic agents to reduce myocardial ischemia is of utmost significance. For the future, it is imperative to enhance our understanding of the pathological mechanism underlying MIRI, continuously investigate and develop novel pharmaceutical agents, expedite the clinical translation of these drugs, and foster innovative approaches that integrate TCM with Western medicine. These efforts will facilitate the emergence of fresh perspectives for the clinical management of MIRI.

The anti-depression effect and potential mechanism of the petroleum ether fraction of CDB: Integrated network pharmacology and metabolomics.

The combination of Chaidangbo (CDB) is an antidepressant traditional Chinese medicine (TCM) prescription simplified by Xiaoyaosan (a classic antidepressant TCM prescription) through dismantling research, which has the effect of dispersing stagnated liver qi and nourishing blood in TCM theory. Although the antidepressant effect of CBD has been confirmed in animal studies, the material basis and possible molecular mechanism for antidepressant activity in CBD have not been clearly elucidated. Herein, we investigated the effects and potential mechanisms of CDB antidepressant fraction (petroleum ether fraction of CDB, PEFC) on chronic unpredictable mild stress (CUMS)-induced depression-like behavior in mice using network pharmacology and metabolomics. First, a UPLC-QE/MS was employed to identify the components of PEFC. To extract active ingredients, SwissADME screening was used to the real PEFC components that were found. Potential PEFC antidepressant targets were predicted based on a network pharmacology approach, and a pathway enrichment analysis was performed for the predicted targets. Afterward, a CUMS mouse depression model was established and LC-MS-based untargeted hippocampal metabolomics was performed to identify differential metabolites, and related metabolic pathways. Finally, the protein expressions in mouse hippocampi were determined by Western blot to validate the network pharmacology and metabolomics deduction. A total of 16 active compounds were screened in SwissADME that acted on 73 core targets of depression, including STAT3, MAPKs, and NR3C1; KEGG enrichment analysis showed that PEFC modulated signaling pathways such as PI3K-Akt signaling pathway, endocrine resistance, and MAPK to exert antidepressant effects. PEFC significantly reversed abnormalities of hippocampus metabolites in CUMS mice, mainly affecting the synthesis and metabolism of glycine, serine, and threonine, impacting catecholamine transfer and cholinergic synapses and regulating the activity of the mTOR signaling pathway. Furthermore, Western blot analysis confirmed that PEFC significantly influenced the main protein levels of the PI3K/Akt/mTOR signaling pathways in the hippocampus of mice subjected to CUMS. This study integrated metabolomics, network pharmacology and biological verification to explore the potential mechanism of PEFC in treating depression, which is related to the regulation of amino acid metabolism dysfunction and the activation of PI3K/Akt/mTOR signaling pathways in the hippocampus. The comprehensive strategy also provided a reasonable way for unveiling the pharmacodynamic mechanisms of multi-components, multi-targets, and multi-pathways in TCM with antidepressant effect.

Traditional Chinese medicine and mitophagy: A novel approach for cardiovascular disease management.

BACKGROUND: Cardiovascular disease (CVD) remains the leading cause of morbidity and mortality worldwide, imposing an enormous economic burden on individuals and human society. Laboratory studies have identified several drugs that target mitophagy for the prevention and treatment of CVD. Only a few of these drugs have been successful in clinical trials, and most studies have been limited to animal and cellular models. Furthermore, conventional drugs used to treat CVD, such as antiplatelet agents, statins, and diuretics, often result in adverse effects on patients' cardiovascular, metabolic, and respiratory systems. In contrast, traditional Chinese medicine (TCM) has gained significant attention for its unique theoretical basis and clinical efficacy in treating CVD. PURPOSE: This paper systematically summarizes all the herbal compounds, extracts, and active monomers used to target mitophagy for the treatment of CVD in the last five years. It provides valuable information for researchers in the field of basic cardiovascular research, pharmacologists, and clinicians developing herbal medicines with fewer side effects, as well as a useful reference for future mitophagy research. METHODS: The search terms "cardiovascular disease," "mitophagy," "herbal preparations," "active monomers," and "cardiac disease pathogenesis" in combination with "natural products" and "diseases" were used to search for studies published in the past five years until January 2024. RESULTS: Studies have shown that mitophagy plays a significant role in the progression and development of CVD, such as atherosclerosis (AS), heart failure (HF), myocardial infarction (MI), myocardial ischemia/reperfusion injury (MI/RI), cardiac hypertrophy, cardiomyopathy, and arrhythmia. Herbal compound preparations, crude extracts, and active monomers have shown potential as effective treatments for these conditions. These substances protect cardiomyocytes by inducing mitophagy, scavenging damaged mitochondria, and maintaining mitochondrial homeostasis. They display notable efficacy in combating CVD. CONCLUSION: TCM (including herbal compound preparations, extracts, and active monomers) can treat CVD through various pharmacological mechanisms and signaling pathways by inducing mitophagy. They represent a hotspot for future cardiovascular basic research and a promising candidate for the development of future cardiovascular drugs with fewer side effects and better therapeutic efficacy.

Preparation technologies, structural features, and biological activities of polysaccharides from Mesona chinensis Benth.: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Mesona chinensis Benth. (or Platostoma palustre (Blume) A. J. Paton) is an important medicinal and edible plant also known as the Hsian-tsao in China and Southeast Asian countries. It is cold in nature and sweet in taste, with the effects of clearing heat, relieving heatstroke and diuretic, and traditionally used to treat heatstroke, erysipelas, hypertension, joint pain and other diseases in folk medicine. It is also a popular supplement with the function of detoxifying and heat-clearing use in Asia. It is used to be processed into the popular tea, Bean jelly, and so on. Published studies have demonstrated that polysaccharides from M. chinensis (MCPs) are one of the principal bioactive ingredients with a variety of health-promoting effects in the prevention and treatment of diseases, including antioxidant, immunomodulation, anti-inflammatory, hepatoprotective, anti-tumor, hypoglycemic, regulation of gut microbiota, and other pharmacological properties. AIM OF THE REVIEW: This review aims to compile the extraction and purification methods, structural characteristics, pharmacological activities including the mechanism of action of MCPs, and to further understand the applications of M. chinensis in order to lay the foundation for the development of MCPs. MATERIALS AND METHODS: By inputting the search term "Mesona chinensis polysaccharides", relevant research information was obtained from databases such as PubMed, Google Scholar, Web of Science, and China National Knowledge Infrastructure (CNKI). RESULTS: More than 40 polysaccharides have been extracted from M. chinensis, different extraction and purification methods have been described, as well as the structural features and pharmacological activities of MCPs have been systematically reviewed. Polysaccharides, as important components of M. chinensis, were mainly extracted by methods such as hot water dipping method, hot alkali extraction method, enzyme-assisted extraction method and ultrasonic-assisted extraction method, subsequently obtained by decolorization, deproteinization, removal of other small molecules and separation on various chromatographic columns. The chemical composition and structure of MCPs show diversity and have a variety of pharmacological activities, including antioxidant, immunomodulation, anti-inflammatory, hepatoprotective, anti-tumor, hypoglycemic, regulation of gut microbiota, and so on. CONCLUSIONS: This article systematically reviews the research progress of MCPs in terms of extraction and purification, structural characteristics, rheological gel properties, pharmacological properties, and safety assessment. The potentials and roles of M. chinensis in the field of medicine, functional food, and materials are further highlighted to provide references and bases for the high-value processing and utilization of MCPs.

The extraction, purification, structural features, bioactivities, and applications of Schisandra chinensis polysaccharides: A review.

Schisandra chinensis, as a famous medicinal and food homologous plant, has a long history of medicinal and dietary therapy. It has the functions of nourishing the kidney, calming the heart, tranquilising the mind, tonifying Qi and producing fluid to relieve mental stress, based on the theory of traditional Chinese medicine. Accumulating evidence has shown that S. chinensis polysaccharides (SCPs) are one of the most important bioactive macromolecules and exhibit diverse biological activities in vitro and in vivo, including neuroprotective, hepatoprotective, immunomodulatory, antioxidant, hypoglycemic, cardioprotective, antitumour and anti-inflammatory activities, etc. This review aims to thoroughly review the recent advances in the extraction and purification methods, structural features, biological activities and structure-activity relationships, potential applications and quality assessment of SCPs, and further highlight the therapeutic potentials and health functions of SCPs in the fields of therapeutic agents and functional food development. Future insights and challenges of SCPs were also critically discussed. Overall, the present review provides a theoretical overview for the further development and utilization of S. chinensis polysaccharides in the health food and pharmaceutical fields.

Extraction techniques, structural features and biological functions of Hippophae rhamnoides polysaccharides: A review.

Hippophae rhamnoides L. (sea buckthorn) is a type of traditional Chinese medicine with a long history of clinical application. It is used in the improvement and treatment of various diseases as medicine and food to strengthen the stomach and digestion, relieving cough and resolving phlegm, promoting blood circulation, and resolving blood stasis in traditional Chinese medicine. Emerging evidence has shown that H. rhamnoides polysaccharides (HRPs) are vital bioactive macromolecules responsible for its various health benefits. HRPs possess the huge potential to develop a drug improving or treating different diseases. In this review, we comprehensively and systematically summarize the recent information on extraction and purification methods, structural features, biological activities, structure-activity relationships, and potential industry applications of HRPs and further highlight the therapeutic potential and sanitarian functions of HRPs in the fields of therapeutic agents and functional food development. Additionally, this paper also lists a variety of biological activities of HRPs in vitro and in vivo roundly. Finally, this paper also discusses the structure-activity relationships and potential applications of HRPs. Overall, this work will help to have a better in-depth understanding of HRPs and provide a scientific basis and direct reference for more scientific and rational applications.

Recent advances in Platycodon grandiflorum polysaccharides: Preparation techniques, structural features, and bioactivities.

Platycodon grandiflorum, a globally recognized medicinal and edible plant, possesses significant nutritional value and pharmacological value. In traditional Chinese medicine, it has the effects of tonifying the spleen and replenishing the Qi, moistening the lung and relieving the cough, clearing the heat and detoxifying, and relieving the pain. Accumulating evidence has revealed that the polysaccharides from P. grandiflorum (PGPs) are one of the major and representative biologically active macromolecules and have diverse biological activities, such as immunomodulatory activity, anti-inflammatory activity, anti-tumor activity, regulation of the gut microbiota, anti-oxidant activity, anti-apoptosis activity, anti-angiogenesis activity, hypoglycemic activity, anti-microbial activity, and so on. Although the polysaccharides extracted from P. grandiflorum have been extensively studied for the extraction and purification methods, structural characteristics, and pharmacological activities, the knowledge of their structures and bioactivity relationship, toxicologic effects, and pharmacokinetic profile is limited. The main purpose of the present review is to provide comprehensively and systematically reorganized information on extraction and purification, structure characterizations, and biological functions as well as toxicities of PGPs to support their therapeutic potentials and sanitarian functions. New valuable insights for future research regarding PGPs were also proposed in the fields of therapeutic agents and functional foods.

Potential therapeutic effects of Chinese herbal medicine in postpartum depression: Mechanisms and future directions.

ETHNOPHARMACOLOGICAL RELEVANCE: Postpartum depression (PPD) is a common psychiatric disorder in women after childbirth. Per data from epidemiologic studies, PPD affects about 5%-26.32% of postpartum mothers worldwide. Biological factors underlying this condition are multiple and complex and have received extensive inquiries for the roles they play in PPD. Chinese herbal medicine (CHM), which is widely used as a complementary and alternative therapy for neurological disorders, possesses multi-component, multi-target, multi-access, and low side effect therapeutic characteristics. CHM has already shown efficacy in the treatment of PPD, and a lot more research exploring the mechanisms of its potential therapeutic effects is being conducted. AIM OF THE REVIEW: This review provides an in-depth and comprehensive overview of the underlying mechanisms of PPD, as well as samples the progress made in researching the potential role of CHM in treating the disorder. MATERIALS AND METHODS: Literature was searched comprehensively in scholarly electronic databases, including PubMed, Web of Science, Scopus, CNKI and WanFang DATA, using the search terms "postpartum depression", "genetic", "hormone", "immune", "neuroinflammation", "inflammation", "neurotransmitter", "neurogenesis", "brain-gut axis", "traditional Chinese medicine", "Chinese herbal medicine", "herb", and an assorted combination of these terms. RESULTS: PPD is closely associated with genetics, as well as with the hormones, immune inflammatory, and neurotransmitter systems, neurogenesis, and gut microbes, and these biological factors often interact and work together to cause PPD. For example, inflammatory factors could suppress the production of the neurotransmitter serotonin by inducing the regulation of tryptophan-kynurenine in the direction of neurotoxicity. Many CHM constituents improve anxiety- and depression-like behaviors by interfering with the above-mentioned mechanisms and have shown decent efficacy clinically against PPD. For example, Shen-Qi-Jie-Yu-Fang invigorates the neuroendocrine system by boosting the hormone levels of hypothalamic pituitary adrenal (HPA) and hypothalamic pituitary gonadal (HPG) axes, regulating the imbalance of Treg/T-helper cells (Th) 17 and Th1/Th2, and modulating neurotransmitter system to play antidepressant roles. The Shenguiren Mixture interferes with the extracellular signal-regulated kinase (ERK) pathway to enhance the number, morphology and apoptosis of neurons in the hippocampus of PPD rats. Other herbal extracts and active ingredients of CHM, such as Paeoniflorin, hypericin, timosaponin B-III and more, also manage depression by remedying the neuroendocrine system and reducing neuroinflammation. CONCLUSIONS: The pathogenesis of PPD is complex and diverse, with the main pathogenesis not clear. Still, CHM constituents, like Shen-Qi-Jie-Yu-Fang, the Shenguiren Mixture, Paeoniflorin, hypericin and other Chinese Medicinal Formulae, active monomers and Crude extracts, treats PPD through multifaceted interventions. Therefore, developing more CHM components for the treatment of PPD is an essential step forward.

Jing-Fang powder ethyl acetate extracts attenuate atopic dermatitis by modulating T-cell activity.

Jing-Fang powder ethyl acetate extract (JFEE) and its isolated C (JFEE-C) possess favorable anti-inflammatory and anti-allergic properties; however, their inhibitory effects on T cell activity remain unknown. In vitro, Jurkat T cells and primary mouse CD4+ T cells were used to explore the regulatory effects of JFEE and JFEE-C as well as their potential mechanisms on activated T cells. Furthermore, T cell-mediated atopic dermatitis (AD) mouse model was established to confirm these inhibitory effects in vivo. The results showed that JFEE and JFEE-C inhibited T cell activation by suppressing the production of interleukin-2 (IL-2) and interferon-gamma (IFN-γ) without showing cytotoxicity. Flow cytometry showed the inhibitory effects of JFEE and JFEE-C on the activation-induced proliferation and apoptosis of T cells. Pretreatment with JFEE and JFEE-C also decreased the expression levels of several surface molecules, including CD69, CD25, and CD40L. Moreover, it was confirmed that JFEE and JFEE-C inhibited T cell activation by downregulating the TGF-ß-activated kinase 1 (TAK1)/nuclear kappa-light-chain-enhancer of activated B cells (NF-κB)/mitogen-activated protein kinase (MAPK) signaling pathways. The combination of these extracts with C25-140 intensified the inhibitory effects on IL-2 production and p65 phosphorylation. The oral administration of JFEE and JFEE-C notably weakened AD manifestations, including the infiltration of mast cells and CD4+ cells, epidermis and dermis thicknesses, serum levels of immunoglobulin E (IgE) and thymic stromal lymphopoietin (TSLP), and gene expression levels of T helper (Th) cells-related cytokines in vivo. The underlying mechanisms of the inhibitory effects of JFEE and JFEE-C on AD were related to attenuating T cell activity through NF-κB/MAPK pathways. In conclusion, this study suggested that JFEE and JFEE-C exhibited anti-atopic efficacy by attenuating T cell activity and might possess a curative potential for T cell-mediated diseases.

[Relationship between pyroptosis and cardiovascular diseases and traditional Chinese medicine prevention and treatment research].

Pyroptosis is a programmed cell death initiated by the activation of caspases, which is involved in the development and progression of several cardiovascular diseases. The gasdermins, a protein family, are key executive proteins in the development of pyroptosis, which increase cell membrane permeability, mediate the release of inflammatory factors, and aggravate the inflammatory injury. Traditional Chinese medicine(TCM)has shown unique therapeutic advantages in cardiovascular diseases with multi-component and multi-target characteristics. Currently, the effective prevention and treatment of cardiovascular diseases based on the theory of pyroptosis become a new research hotspot in this field. Based on the theories of TCM and modern medicine, this study summarized the role of pyroptosis in cardiovascular diseases such as atherosclerosis, myocardial infarction, diabetic cardiomyopathy, hypertension, and myocarditis. The role of TCM, including active monomers, crude extracts, and compound preparations, in cardiovascular protection through the regulation of pyroptosis was also summarized, providing a theoretical basis for the clinical prevention and treatment of cardiovascular diseases by TCM.

[Experimental study of cardioprotective effects of Cinnamomi Ramulus and Cinnamomi Cortex formula granules on myocardial ischemia/reperfusion injury in rats based on efficacy of "warming and coordinating heart Yang"].

This study aimed to parallelly investigate the cardioprotective activity of Cinnamomi Ramulus formula granules(CRFG) and Cinnamomi Cortex formula granules(CCFG) against acute myocardial ischemia/reperfusion injury(MI/RI) and the underlying mechanism based on the efficacy of "warming and coordinating the heart Yang". Ninety male SD rats were randomly divided into a sham group, a model group, CRFG low and high-dose(0.5 and 1.0 g·kg~(-1)) groups, and CCFG low and high-dose(0.5 and 1.0 g·kg~(-1)) groups, with 15 rats in each group. The sham group and the model group were given equal volumes of normal saline by gavage. Before modeling, the drug was given by gavage once a day for 7 consecutive days. One hour after the last administration, the MI/RI rat model was established by ligating the left anterior descending artery(LAD) for 30 min ischemia followed by 2 h reperfusion except the sham group. The sham group underwent the same procedures without LAD ligation. Heart function, cardiac infarct size, cardiac patho-logy, cardiomyocyte apoptosis, cardiac injury enzymes, and inflammatory cytokines were determined to assess the protective effects of CRFG and CCFG against MI/RI. The gene expression levels of nucleotide-binding oligomerization domain-like receptor family pyrin domain protein 3(NLRP3) inflammasome, apoptosis-associated speck-like protein containing a CARD(ASC), cysteinyl aspartate specific proteinase-1(caspase-1), Gasdermin-D(GSDMD), interleukin-1ß(IL-1ß), and interleukin-18(IL-18) were determined by real-time quantitative polymerase chain reaction(RT-PCR). The protein expression levels of NLRP3, caspase-1, GSDMD, and N-GSDMD were determined by Western blot. The results showed that both CRFG and CCFG pretreatments significantly improved cardiac function, decreased the cardiac infarct size, inhibited cardiomyocyte apoptosis, and reduced the content of lactic dehydrogenase(LDH), creatine kinase MB isoenzyme(CK-MB), aspartate transaminase(AST), and cardiac troponin Ⅰ(cTnⅠ). In addition, CRFG and CCFG pretreatments significantly decreased the levels of IL-1ß, IL-6, and tumor necrosis factor-α(TNF-α) in serum. RT-PCR results showed that CRFG and CCFG pretreatment down-regulated the mRNA expression levels of NLRP3, caspase-1, ASC, and downstream pyroptosis-related effector substances including GSDMD, IL-18, and IL-1ß in cardiac tissues. Western blot revealed that CRFG and CCFG pretreatments significantly decreased the protein expression levels of NLRP3, caspase-1, GSDMD, and N-GSDMD in cardiac tissues. In conclusion, CRFG and CCFG pretreatments have obvious cardioprotective effects on MI/RI in rats, and the under-lying mechanism may be related to the inhibition of NLRP3/caspase-1/GSDMD signaling pathway to reduce the cardiac inflammatory response.

Crataegus pinnatifida: A botanical, ethnopharmacological, phytochemical, and pharmacological overview.

ETHNOPHARMACOLOGICAL RELEVANCE: Crataegus pinnatifida belongs to the Rosaceae family and extensively distribute in North China, Europe, and North America. Its usage was first described in "Xinxiu Ben Cao." The dried fruits of Crataegus pinnatifida Bunge or Crataegus pinnatifida var. major N. E. Br., also known as "Shanzha," is a famous medicine and food homology herb with a long history of medicinal usage in China. C. pinnatifida has the functions for digestive promotion, cardiovascular protection, and lipid reduction. It was traditionally used to treat indigestion, cardiodynia, thoracalgia, hernia, postpartum blood stagnation, and hemafecia. In recent years, C. pinnatifida has attracted worldwide attention as an important medicinal and economical crop due to its multiple and excellent health-promoting effects on cardiovascular, nervous, digestive, endocrine systems, and morbigenous microorganisms of the human body due to its medicinal and nutritional values. AIM OF THE REVIEW: The current review aims to provide a comprehensive analysis of the geographical distribution, traditional usage, phytochemical components, pharmacological actions, clinical settings, and toxicities of C. pinnatifida. Moreover, the connection between the claimed biological activities and the traditional usage, along with the future perspectives for ongoing research on this plant, were also critically summarized. MATERIALS AND METHODS: We collected the published literature on C. pinnatifida using a variety of scientific databases, including Web of Science, ScienceDirect, PubMed, Wiley, Springer, Taylor & Francis, ACS Publications, Google Scholar, Baidu Scholar, CNKI, The Plant List Database, and other literature sources (Ph.D. and MSc dissertations) from 2012 to 2022. RESULTS: In the last decade, over 250 phytochemical compounds containing lignans, phenylpropanoids, flavonoids, triterpenoids, and their glycosides, as well as other compounds, have been isolated and characterized from different parts, including the fruit, leaves, and seeds of C. pinnatifida. Among these compounds, flavonoids and triterpenoids were major bioactive components of C. pinnatifida. They exhibited a broad spectrum of pharmacological actions with low toxicity in vitro and in vivo, such as cardiovascular protection, neuroprotection, anti-inflammatory, antioxidant, antibacterial, antiviral, anti-diabetes, anti-cancer, anti-mutagenic, anti-osteoporosis, anti-aging, anti-obesity, and hepatoprotection and other actions. CONCLUSION: A long history of traditional uses and abundant pharmacochemical and pharmacological investigations have demonstrated that C. pinnatifida is an important medicine and food homology herb, which displays outstanding therapeutic potential, especially in the digestive system and cardiovascular disease. Nevertheless, the current studies on the active ingredients or crude extracts of C. pinnatifida and the possible mechanism of action are unclear. More evidence-based scientific studies are required to verify the traditional uses of C. pinnatifida. Furthermore, more efforts must be paid to selecting index components for quality control research and toxicity and safety studies of C. pinnatifida.

Several Alkaloids in Chinese Herbal Medicine Exert Protection in Acute Kidney Injury: Focus on Mechanism and Target Analysis.

Objectives: Acute kidney injury (AKI) is a loose set of kidney diseases accompanied by a variety of syndromes, which is a serious threat to human life and health. Some alkaloids are derived from various Chinese herbs have been widely concerned in the improvement of AKI. This review provides the research progress of alkaloids in AKI experimental models and discusses the related molecular mechanisms. Key Findings. Alkaloids can protect AKI through various mechanisms including antioxidant stress, improvement of mitochondrial damage, reduction of cell death, induction of autophagy, and inhibition of inflammation. These mechanisms are mainly related to the activation of Nrf2/HO-1 signaling pathway, inhibition of ferroptosis and apoptosis, regulation of PINK1/Parkin pathway, inhibition of TLR4/NF-κB pathway and NLRP3 inflammatory bodies, upregulation of Klotho protein level and so on. In addition, there are a few alkaloids that have certain toxicity on the kidney. Conclusion: Alkaloids have been shown to significantly improve AKI, but only in pharmacological studies. This paper summarizes the main experimental models currently used in AKI research and describes some representative alkaloids based on recent research. Their potential roles in the prevention and treatment of AKI through different mechanisms are highlighted.

Traditional uses, phytochemical constituents and pharmacological properties of Osmanthus fragrans: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Osmanthus fragrans Lour., is a medicinal plant distributed widely in some Asian countries including Japan and Korea and southwestern China. It has been used traditionally for the treatment of weakened vision, halitosis, panting, asthma, cough, toothache, stomachache, diarrhea, rheumatism, physique pain and hepatitis. AIM OF THE REVIEW: Recent advances in traditional uses, botanical characteristics, distribution, taxonomy, phytochemical constituents, biological effects as well as the toxicities of O. fragrans are comprehensively presented and critically evaluated, and the underlying mechanism associated with the bioactivities of extracts, essential oil and components from this plant is also well summarized. In order to provide comprehensive scientific basis for the medical application and help interested researchers discover food and medicinal natural products from O. fragrans. MATERIALS AND METHODS: All information was systematically gathered from globally accepted scientific databases by Internet databases, including Elsevier, ScienceDirect, PubMed, Web of Science, Wiley, Springer, SciFinder, ACS Publications, CNKI, WanFang, Google Scholar, Baidu Scholar, The Plant List Database, and other literature sources (Ph.D. and MSc dissertations). All published contributions on O. fragrans different languages were included and cited. The chemical structures of all isolated compounds were drawn by using ChemBioDraw Ultra 14.0 software. RESULTS: To date, more than 183 compounds were isolated and structurally identified from different plant parts of O. fragrans. Among them, ionone, ionol, flavonoids, polyphenols and iridoids, as the major bioactive substances, have been extensively studied and displayed the best bioactivity. Pharmacological studies demonstrated that O. fragrans and its active components had a wide range of biological activities, such as antioxidant, antitumor, anti-inflammatory, anti-hyperglycemic, anti-thrombotic, anti-melanogenesis, neuroprotective, and hepatoprotective activities, etc. CONCLUSION: O. fragrans, as a food and medicinal resource, has a good health care function and important edible and medicinal value, and thus has good prospects for utilization. However, many studies on biological activities were mainly based on extracts and the bioactive ingredients of this plant, and the mechanism responsible for these extracts and ingredients have not been well identified and there is a gap in research regarding clinical effect and safety. Therefore, the detail in vitro and in vivo studies on the mechanisms of action of the pure bioactive compounds and more clinical studies are encouraged to be conducted to ensure safety and effectiveness of the plant for human use.

Cinnamic acid preserves against myocardial ischemia/reperfusion injury via suppression of NLRP3/Caspase-1/GSDMD signaling pathway.

BACKGROUND: Cinnamic acid (CA) is an active organic acid compound extracted from Cinnamomi ramulus that has various biological activities. There is growing studies have shown that the nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome significantly contributes to sterile inflammatory response and pyroptosis in myocardial ischemia/reperfusion injury (MI/RI). However, whether CA has any influence on NLRP3 inflammasome and pyroptosis during MI/RI are not fully elucidated. PURPOSE: In the present study, we investigated whether NLRP3 inflammasome activation and pyroptosis were involved in the cardioprotective effect of CA against MI/RI. METHODS: Male Sprague-Dawley rats were intragastrically administered either with CA (75 and 150 mg/kg, daily) or vehicle for 7 successive days prior to ligation of coronary artery, and then rats were subjected to ligation of the left anterior descending coronary artery for 30 min followed by reperfusion for 120 min to evoke MI/RI. RESULTS: Our results demonstrated that CA could significantly improve cardiac diastolic function, decrease cardiac infarct size and myocardial injury enzymes, inhibit cardiomyocyte apoptosis, attenuate cardiac structure abnormality, and mitigate oxidative stress and inflammatory response. We also found that MI/RI activate NLRP3 inflammasome as evidenced by the upregulation levels of NLRP3, pro-caspase-1, caspase-1, and ASC proteins and mRNA. More importantly, MI/RI trigger pyroptosis as indicated by increased DNA fragmentation, membrane pore formation, and mitochondrial swelling as well as increased levels of pyroptosis-related proteins and mRNA, including GSDMD, N-GSDMD, IL-18, and IL-1ß. As expected, all these deleterious alterations were prominently reversed by CA pretreatment. CONCLUSIONS: These findings indicate that CA effectively protected cardiomyocytes against MI/RI by inhibiting NLRP3/Caspase-1/GSDMD signaling pathway, and it is worthy of more investigations for its therapeutic potential for extenuating ischemic heart disease.

Alpinetin: A Review of Its Pharmacology and Pharmacokinetics.

Flavonoids isolated from medicinal herbs have been utilized as valuable health-care agents due to their virous biological applications. Alpinetin is a natural flavonoid that emerges in many widely used medicinal plants, and has been frequently applied in Chinese patent drugs. Accumulated evidence has demonstrated that alpinetin possesses a broad range of pharmacological activities such as antitumor, antiinflammation, hepatoprotective, cardiovascular protective, lung protective, antibacterial, antiviral, neuroprotective, and other properties through regulating multiple signaling pathways with low systemic toxicity. However, pharmacokinetic studies have documented that alpinetin may have poor oral bioavailability correlated to its extensive glucuronidation. Currently, the reported pharmacological properties and pharmacokinetics profiles of alpinetin are rare to be scientifically reviewed. In this article, we aimed to highlight the mechanisms of action of alpinetin in various diseases to strongly support its curative potentials for prospective clinical applications. We also summarized the pharmacokinetics properties and proposed some viable strategies to convey an appreciable reference for future advances of alpinetin in drug development.

Xiaoyaosan ethyl acetate fraction alleviates depression-like behaviors in CUMS mice by promoting hippocampal neurogenesis via modulating the IGF-1Rß/PI3K/Akt signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaoyaosan (XYS), a representative and classic traditional Chinese medicine (TCM) prescription with function of dispersing stagnated liver and strengthening spleen, has been used for thousands of years to treat depression. XYS' anti-depression effect has been demonstrated both clinically and experimentally; however, the material basis for this effect has yet to be elucidated. AIM OF THE STUDY: This study aimed to evaluate the impact and underlying action mechanism of XYS' antidepressant active component (Xiaoyaosan ethyl acetate fraction, XYSEF) against chronic unpredictable mild stress (CUMS)-induced depression-like behavior in mice. MATERIALS AND METHODS: First, we established a behavioral despair depression mouse model to preliminarily determine the effective antidepressant dose of XYSEF. Then, we created a CUMS mouse model and used various classic behavioral tests, including SPT, ST, NFST, and TST, to assess XYSEF's antidepressant properties. IGF-1 levels in mouse serum and hippocampus were quantified using ELISA. The average optical density of Nissl bodies in the mouse hippocampal CA3 region was determined utilizing toluidine blue staining. Brdu and DCX expression in the hippocampal dentate gyrus (DG) was assayed using the immunofluorescence method. IGF-1Rß, PI3K, p-PI3K, Akt, p-Akt, Caspase-3, and cleaved Caspase-3 protein levels in the hippocampus were determined with Western blot. RESULTS: The behavioral despair mouse model findings showed that 9.1 and 40 g/kg of XYSEF both significantly shortened the immobility time of mice, suggesting that the effective dose range was 9.1-40 g/kg. Compared to the CUMS mouse model, XYSEF at 20 and 40 g/kg markedly increased the sucrose preference percentage in the SPT and grooming time in the ST, shortened the immobility time in the TST and the feeding latency in the NSFT, and reversed the downregulated IGF-1 content in mouse serum and hippocampus. In addition, XYSEF amplified the average optical density of Nissl bodies in the hippocampal CA3 region, promoted Brdu and DCX expression in DG, and diminished IGF-1Rß, p-PI3K/PI3K, p-Akt/Akt, and cleaved Caspase-3/Caspase-3 protein levels in the hippocampi of CUMS mice. CONCLUSION: XYSEF acted as an antidepressant in mice exhibiting CUMS-induced depression-like behaviors, possibly by promoting hippocampal neurogenesis, reducing neuronal apoptosis, and inhibiting the over-activation of the IGF-1Rß/PI3K/Akt pathway.

JFNE-A isolated from Jing-Fang n-butanol extract attenuates lipopolysaccharide-induced acute lung injury by inhibiting oxidative stress and the NF-κB signaling pathway via promotion of autophagy.

BACKGROUND: Jing-Fang powder consists of Jingjie (Nepeta tenuifolia Benth, (Lamiaceae)). and Fangfeng (Saposhnikovia divaricata (Turcz.) Schischk, (Apiaceae)) Previous studies have revealed that the Jing-Fang powder n-butanol extract (JFNE) has anti-acute lung injury (ALI) and anti-inflammatory properties; however, the active ingredient and mechanism remain unknown. PURPOSE: In the present study, we investigated the anti-inflammatory effect of a bioactive fraction obtained from JFNE(JFNE-A) on lipopolysaccharide (LPS)-induced ALI in mice and explored the underlying mechanism. STUDY DESIGN: The anti-acute lung injury effect and mechanism of JFNE-A was investigated by prophylactic administration of JFNE-A in mice with LPS-induced acute lung injury. METHODS: The expression levels of myeloperoxidase(MPO) in lung tissues of mice and interleukin(IL)-6, tumor necrosis factor(TNF)-α, IL-1ß, IL-5, interferon (IFN)-γ, monocyte chemotactic protein (MCP)-1, macrophage colony stimulating factor (M-CSF), macrophage inflammatory protein (MIP)-1α, and MIP-1ß in bronchi alveolar lavage fluid (BALF) were detected by reagent kit and the histological changes were examined by hematoxylin and eosin (H & E) for general histopathological conditions under a light microscope. In addition, the ultrastructure of the cells in lung tissues were observed and photographed under a transmission electron microscope. The expression levels of protein were detected via Western blotting and the mRNA expression of relative genes were determined of via reverse transcriptase polymerase chain reaction (RT-PCR). What's more, we also further clarified the potential targets of JFNE-A through network pharmacology analysis, which could be utilized in ALI treatment. RESULTS: Our results showed that pretreatment with JFNE-A for 7 days significantly reduced the lung pathological injury score, alleviated pulmonary edema, and decreased the lung tissue MPO level. Mechanistically, JFNE-A dramatically downregulated the protein levels of IL-6, TNF-α, IL-1ß, M-CSF, and IFN-γ in BALF and mRNA expression levels of IL-6, TNF-α, IL-1ß, and IFN-γ in lung tissues. JFNE-A also significantly lowered the protein levels of iNOS and phosphorylated NF-κB (p65) and mRNA expression levels of iNOS, Rela, CHUK, and NF-κB1, and also elevated the protein expression levels of Nrf2, HO-1, and SOD1 and the mRNA expression levels of Nrf2, Hmox1, and Keap-1 in the lungs. Moreover, JFNE-A significantly decreased the protein expression of p62 and increased the ratio of LC3II/LC3I. It also upregulated the mRNA expression levels of Atg5 and Beclin-1, whereas it reduced the mRNA expression level of SQSTM1 and increased autophagosome structures. CONCLUSION: Overall, treatment with JFNE-A ameliorated LPS-induced ALI in mice by suppressing the NF-κB signaling pathways and promoting Nrf2 signaling pathways by accelerating autophagy.

Research Progress in the Pharmacological Activities, Toxicities, and Pharmacokinetics of Sophoridine and Its Derivatives.

Sophoridine is a natural quinolizidine alkaloid and a bioactive ingredient that can be isolated and identified from certain herbs, including Sophora flavescens Alt, Sophora alopecuroides L, and Sophora viciifolia Hance. In recent years, this quinolizidine alkaloid has gained widespread attention because of its unique structure and minimal side effects. Modern pharmacological investigations have uncovered sophoridine's multiple wide range biological activities, such as anti-cancer, anti-inflammatory, anti-viral, anti-arrhythmia, and analgesic functions, among others. These pharmacological activities and beneficial effects point to sophoridine as a strong potential therapeutic candidate for the treatment of various diseases, including several cancer types, hepatitis B virus, enterovirus 71, coxsackievirus B3, cerebral edema, cancer pain, heart failure, acute myocardial ischemia, arrhythmia, inflammation, acute lung injury, and osteoporosis. The data showed that sophoridine had adverse reactions, including hepatotoxicity and neurotoxicity. Additionally, analyses of sophoridine's safety, bioavailability, and pharmacokinetic parameters in animal models of research have been limited, especially in the clinic, as have been investigations on its structure-activity relationship. In this article, we comprehensively summarize the biological activities, toxicity, and pharmacokinetic characteristics of sophoridine and its derivatives, as currently reported in publications, as we attempt to provide an overall perspective on sophoridine analogs and the prospects of its application clinically.