Emerging insights into traditional Chinese medicine associated with neurodegenerative diseases: A bibliometric analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: Research suggests that traditional Chinese medicine (TCM) holds promise in offering innovative approaches to tackle neurodegenerative disorders. In our endeavor, we conducted a comprehensive bibliometric analysis to delve into the landscape of TCM research within the realm of neurodegenerative diseases, aiming to uncover the present scenario, breadth, and trends in this field. This analysis presents potentially valuable insights for the clinical application of traditional Chinese medicine and provides compelling evidence supporting its efficacy in the treatment of neurodegenerative conditions. AIM OF THE STUDY: The incidence of neurodegenerative diseases is on the rise, yet effective treatments are still lacking. Research indicates that TCM could offer novel perspectives for addressing neurodegenerative conditions. Nonetheless, the literature on this topic is intricate and multifaceted, with existing reviews offering only limited coverage. To gain a thorough understanding of TCM research in neurodegenerative diseases, we undertook a bibliometric analysis to explore the current status, scope, and trends in this area. MATERIALS AND METHODS: A literature search was carried out on April 1, 2024, utilizing the Web of Science Core Collection (WoSCC). Visualization and quantitative analyses were then performed with the assistance of CiteSpace, VOSviewer, and R software. RESULTS: A total of 6856 articles were retrieved in the search. Research on TCM for neurodegenerative diseases commenced in 1989 and has exhibited a notable overall growth since then. Main research contributors include East Asian countries like China, as well as the United States. Through our analysis, we identified 15 highly productive authors, 10 top-tier journals, 13 citation clusters, 11 influential articles, and observed a progression in keyword evolution across 4 distinct categories. In 2020, there was a significant upsurge in the knowledge base, collaboration efforts, and publication output within the field. This field is interdisciplinary: network pharmacology emerges as the cutting-edge paradigm in TCM research, while Alzheimer's disease remains a prominent focus among neurodegenerative conditions due to its evolving etiology. A burst detection analysis unveils that in 2024, the focal points of research convergence between TCM and neurodegenerative diseases lie in two key biological processes or mechanisms: autophagy and microbiota. CONCLUSIONS: For the first time, this study quantitatively and visually captures the evolution of TCM in addressing neurodegenerative diseases, showcasing a notable acceleration in recent years. Our findings underscore the pivotal role of interdisciplinary collaboration and the necessity for increased global partnerships. Network pharmacology, leveraging the advancements of the big data era, embraces a holistic and systematic approach as a novel paradigm in exploring traditional Chinese medicine and unraveling their fundamental mechanisms. Three ethnomedical plants-Tianma, Renshen, and Wuweizi-demonstrate the promise of their bioactive compounds in treating neurodegenerative disorders, bolstered by their extensive historical usage for such ailments. Moreover, our intricate analysis of the evolutionary trajectories of key themes such as targets and biomarkers substantially enriches our comprehension of the underlying mechanisms involved.

Multi-layered effects of Panax notoginseng on immune system.

Recent research has demonstrated the immunomodulatory potential of Panax notoginseng in the treatment of chronic inflammatory diseases and cerebral hemorrhage, suggesting its significance in clinical practice. Nevertheless, the complex immune activity of various components has hindered a comprehensive understanding of the immune-regulating properties of Panax notoginseng, impeding its broader utilization. This review evaluates the effect of Panax notoginseng to various types of white blood cells, elucidates the underlying mechanisms, and compares the immunomodulatory effects of different Panax notoginseng active fractions, aiming to provide the theory basis for future immunomodulatory investigation.

Mitofilin in cardiovascular diseases: Insights into the pathogenesis and potential pharmacological interventions.

The impact of mitochondrial dysfunction on the pathogenesis of cardiovascular disease is increasing. However, the precise underlying mechanism remains unclear. Mitochondria produce cellular energy through oxidative phosphorylation while regulating calcium homeostasis, cellular respiration, and the production of biosynthetic chemicals. Nevertheless, problems related to cardiac energy metabolism, defective mitochondrial proteins, mitophagy, and structural changes in mitochondrial membranes can cause cardiovascular diseases via mitochondrial dysfunction. Mitofilin is a critical inner mitochondrial membrane protein that maintains cristae structure and facilitates protein transport while linking the inner mitochondrial membrane, outer mitochondrial membrane, and mitochondrial DNA transcription. Researchers believe that mitofilin may be a therapeutic target for treating cardiovascular diseases, particularly cardiac mitochondrial dysfunctions. In this review, we highlight current findings regarding the role of mitofilin in the pathogenesis of cardiovascular diseases and potential therapeutic compounds targeting mitofilin.

Complex components of Shengmai formula interact with organic cation transporter 2 (OCT2) in MDCK cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Shengmai formula (SMF) is a well-known Chinese herbal compound preparation, which is utilized extensively for the treatment of myocardial ischemia, arrhythmia and other life-threatening conditions. Our previous researches have shown that some of the active ingredients in SMF can interact with organic anion transport polypeptide 1B1 (OATP1B1), breast cancer resistance protein (BCRP) and organic anion transporter 1 (OAT1), etc. Organic cation transporter 2 (OCT2) is a highly expressed uptake transporter in the kidney, and its interaction with the major active components in SMF remains unclear. AIM OF THE STUDY: We purposed to explore OCT2-mediated interactions and compatibility mechanisms of the main active compounds in SMF. MATERIALS AND METHODS: Fifteen active ingredients of SMF, including ginsenoside Rb1, Rd, Re, Rg1, Rf, Ro and Rc, methylophiopogonanone A and B, ophiopogonin D and D', schizandrin A and B, schizandrol A and B, were selected to investigate OCT2-mediated interactions in Madin-Darby cacine kidney (MDCK) cells stably expressing OCT2. RESULTS: Among the above 15 main active components, only ginsenosides Rd, Re and schizandrin B could significantly inhibit the uptake of 4-(4-(dimethylamino)styryl)-N-methyl pyridiniumiodide (ASP+), a classical substrate of OCT2. Ginsenoside Rb1 and methylophiopogonanone A can be transported by MDCK-OCT2 cells, and their uptake was significantly reduced when OCT2 inhibitor decynium-22 was added. Ginsenoside Rd could remarkably reduce the uptake of methylophiopogonanone A and ginsenoside Rb1 by OCT2, ginsenoside Re only decreased the uptake of ginsenoside Rb1, while schizandrin B had no effect on the uptake of both. CONCLUSIONS: OCT2 mediates the interaction of the major active components in SMF. Ginsenosides Rd, Re and schizandrin B are the potential inhibitors of OCT2, while ginsenosides Rb1 and methylophiopogonanone A are the potential substrates of OCT2. There is an OCT2-mediated compatibility mechanism among these active ingredients of SMF.

Saponins and their derivatives: Potential candidates to alleviate anthracycline-induced cardiotoxicity and multidrug resistance.

Anthracyclines (ANTs) continue to play an irreplaceable role in oncology treatment. However, the clinical application of ANTs has been limited. In the first place, ANTs can cause dose-dependent cardiotoxicity such as arrhythmia, cardiomyopathy, and congestive heart failure. In the second place, the development of multidrug resistance (MDR) leads to their chemotherapeutic failure. Oncology cardiologists are urgently searching for agents that can both protect the heart and reverse MDR without compromising the antitumor effects of ANTs. Based on in vivo and in vitro data, we found that natural compounds, including saponins, may be active agents for other both natural and chemical compounds in the inhibition of anthracycline-induced cardiotoxicity (AIC) and the reversal of MDR. In this review, we summarize the work of previous researchers, describe the mechanisms of AIC and MDR, and focus on revealing the pharmacological effects and potential molecular targets of saponins and their derivatives in the inhibition of AIC and the reversal of MDR, aiming to encourage future research and clinical trials.

Interaction of the main active components in Shengmai formula mediated by organic anion transporter 1 (OAT1).

ETHNOPHARMACOLOGICAL RELEVANCE: Shengmai formula (SMF) is a classical traditional Chinese medicine prescription, which is widely used in the treatment of cardiovascular and cerebrovascular diseases. Our previous studies have demonstrated that some components in SMF can interact with each other through breast cancer resistance protein, sodium taurocholate co-transporting polypeptide, organic anion transporting polypeptide 1B1 and 1B3. Organic anion transporter 1 (OAT1) is highly expressed in kidney, mediating the elimination of many endogenous and exogenous substances. However, the interaction between the main active components in SMF and OAT1 is not clear. AIM OF THE STUDY: This study aimed to investigate the interactions of the major bioactive components in SMF mediated by OAT1. MATERIALS AND METHODS: Four main fractions, namely, ginseng total saponins (GTS), ophiopogon total saponins (OTS), ophiopogon total flavonoids (OTF), fructus schisandrae total lignans (STL), and 12 active components, namely, ginsenoside Rg1, Re, Rd and Rb1, ophiopogonin D and D', methylophiopogonanone A and B, schizandrol A and B, schizandrin A and B, were selected to explore the interactions of SMF with OAT1 using cell and rat models. RESULTS: The above four main fractions in SMF all exhibited inhibitory effects on the uptake of 6-carboxyfluorescein (6-CF), a classic substrate of OAT1. Among the 12 main effective components, only ginsenoside Re, Rd, and methylophiopogonanone A showed inhibition of 6-CF uptake. Additionally, we found that schizandrin B was transported by HEK293-OAT1 cells, and schizandrin B uptake was markedly inhibited by GTS, OTS, OTF, ginsenoside Re, Rd, and methylophiopogonanone A. In rats, ginsenoside Re, Rd, and methylophiopogonanone A jointly increased the AUC(0-t), AUC(0-∞), and Cmax of schizandrin B, but they decreased its clearance in plasma and excretion in urine. CONCLUSIONS: Ginsenoside Re, Rd, and methylophiopogonanone A were the potential inhibitors of OAT1, and may interact with some drugs serving as OAT1 substrates clinically. Schizandrin B was a potential OAT1 substrate, and its OAT1-mediated transport was inhibited by ginsenoside Re, Rd, and methylophiopogonanone A. OAT1-mediated interactions of the main active components in SMF can be regarded as one of the important compatibility mechanisms of traditional Chinese medicine preparations.

Progress in the treatment of drug-induced liver injury with natural products.

There are numerous prescription drugs and non-prescription drugs that cause drug-induced liver injury (DILI), which is the main cause of liver disease in humans around the globe. Its mechanism becomes clearer as the disease is studied further. For an instance, when acetaminophen (APAP) is taken in excess, it produces N-acetyl-p-benzoquinone imine (NAPQI) that binds to biomacromolecules in the liver causing liver injury. Treatment of DILI with traditional Chinese medicine (TCM) has shown to be effective. For example, activation of the Nrf2 signaling pathway as well as regulation of glutathione (GSH) synthesis, coupling, and excretion are the mechanisms by which ginsenoside Rg1 (Rg1) treats APAP-induced acute liver injury. Nevertheless, reducing the toxicity of TCM in treating DILI is still a problem to be overcome at present and in the future. Accumulated evidences show that hydrogel-based nanocomposite may be an excellent carrier for TCM. Therefore, we reviewed TCM with potential anti-DILI, focusing on the signaling pathway of these drugs' anti-DILI effect, as well as the possibility and prospect of treating DILI by TCM based on hydrogel materials in the future. In conclusion, this review provides new insights to further explore TCM in the treatment of DILI.

Targeting Akt/CREB/BDNF signaling pathway by ginsenosides in neurodegenerative diseases: A mechanistic approach.

Neurodegenerative diseases (NDDs) are leading causes of death and morbidity in the elderly worldwide. From the mechanistic/pathological view, oxidative stress, inflammation, and apoptosis are responsible for the etiology of neuronal diseases, and play detrimental roles in neuronal cell death and neurodegenerative processes. The diverse pathophysiological pathways influencing NDDs necessitate the discovery of pivotal dysregulated signaling mediators. The current review describes essential functions of protein kinase B (Akt)/cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathway as possible therapeutic targets in the pathogenesis of NDDs. Consequently, finding new multi-target agents in regulating Akt/CREB/BDNF and thus associated downstream pathways is a critical factor in combating NDDs. Because of their neuroprotective properties, dietary phytochemicals have shown to be popular nutritional therapy methods. Ginsenosides, the most active ingredient of ginseng, and a secondary metabolite of steroid glycosides and triterpene saponins have been found to have a number of protective effects on the central nervous system (CNS). The protective roles of ginsenosides in CNS are potentially passing through Akt/CREB/BDNF pathway towards neuroprotective responses. In the present study, Akt/CREB/BDNF pathway is targeted by ginsenosides and associated nanoformulations towards potential neuroprotective effects.

Chinese patent medicine Aidi injection for cancer care: An overview of systematic reviews and meta-analyses.

ETHNOPHARMACOLOGICAL RELEVANCE: Aidi injection is one of the China Food and Drug Administration approved Chinese herbal injections and the most competitive product in cancer care in China. It is composed of the extracts from Mylabris Phalerata, Astragalus Membranaceus, Panax Ginseng, and Acanthopanax Senticosus. AIM OF THE STUDY: This overview aims to map systematic reviews (SRs) of Aidi injection for cancer and provide a summarized evidence for clinical practice and decision making. MATERIALS AND METHODS: Seven databases were searched for SRs and/or meta-analyses of randomized controlled trials on Aidi injection for cancer care until December 2020. Six authors worked in pairs independently identified studies, collected data, and assessed the quality of included studies according to the revised Assessment of Multiple Systematic Reviews (AMSTAR 2) and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). A narrative synthesis was used for the evidence mapping. RESULTS: Fifty-two SRs on Aidi injection as adjuvant therapy were included, involving lung cancer (20 SRs), liver cancer (10), colorectal cancer (7), gastric cancer (6), lymphoma (2), breast cancer (2), esophageal cancer (1), ovary cancer (1), and a mix of different cancers (4). Except for one SR focusing on Aidi injection used alone, other SRs evaluated Aidi injection in combination with chemotherapy (43), radiotherapy (4), or chemo/radiology/targeting therapy (4). Aidi injection showed additional beneficial effects on survival (9), objective response rate (44), quality of life (42), and the reduction of side-effects from chemo/radiotherapy (48). Using AMSTAR 2 tool, two reviews were assessed as low and the rest as critically low methodological quality mainly due to the lack of prospective registration. The reporting quality was insufficient assessed with PRISMA in the reporting of search strategy (26, 50.0%), additional analysis (19, 36.5%), and the summary of evidence (2, 3.8%). CONCLUSION: Aidi injection has been evaluated for its adjuvant beneficial effects on cancer survival, tumor responses, quality of life, and reducing the side effects of chemo/radiotherapy, mainly focusing on lung, liver and colorectal cancer. The methodological and reporting quality are weak and need to be improved in the future.

Ginsenosides in vascular remodeling: Cellular and molecular mechanisms of their therapeutic action.

Evidence is mounting that abnormal vascular remodeling (VR) is a vital pathological event that precedes many cardiovascular diseases (CVD). This provides us with a new research perspective that VR can be a pivotal target for CVD treatment and prevention. However, the current drugs for treating CVD do not fundamentally reverse VR and repair vascular function. The reason may be that a complicated regulatory network is formed between the various signaling pathways involved in VR. Recently, ginsenoside, the main active substance of ginseng, has become increasingly the focus of many researchers for its multiple targets, multiple pathways, and few side effects. Several data have revealed that ginsenosides can improve VR caused by vasodilation dysfunction, abnormal vascular structure and blood pressure. This review is intended to discuss the therapeutic effects and mechanisms of ginsenosides in some diseases involved in VR. Besides, we herein also give a new and contradictory insight into intracellular and molecular signaling of ginsenosides in all kinds of vascular cells. Most importantly, we also discuss the feasibility of ginsenosides Rb1/Rg1/Rg3 in drug development by combining the pharmacodynamics and pharmacokinetics of ginsenosides, and provide a pharmacological basis for the development of ginsenosides in clinical applications.

The dual roles of ginsenosides in improving the anti-tumor efficiency of cyclophosphamide in mammary carcinoma mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Cyclophosphamide (CTX) is a first line chemotherapeutic agent, but often limited for its unstable therapeutic effect and serious side effects. Ginsenosides could facilitate the anti-tumor efficiency of CTX, including benefiting therapeutic effect and decreasing side effects. AIM OF THE STUDY: To investigate the potential mechanism of ginsenosides on benefiting the anti-tumor efficiency of CTX. MATERIALS AND METHODS: Mammary carcinoma mice were applied to investigate the anti-tumor efficiency and potential mechanism of combinational treatment of ginsenosides and CTX. Therapeutic effect was evaluated based on survival rate, tumor burden, tumor growth inhibition rate, and apoptosis and histological changes of tumor tissues. Anti-tumor immunity was studied by measuring serum level of anti-tumor cytokines. Gut mucositis, one of lethal side effects of CTX, was evaluated by diarrhea degree, gut permeability and tight junction proteins expressions. Gut microbial diversity was analyzed by 16S rRNA gene sequencing, and fecal transplant and antibiotics sterilized animals were performed to evaluate the therapeutic effect of gut microbiota on tumor suppression. RESULTS: Ginsenosides facilitated the therapeutic effect of CTX in mice, which manifested as prolonged survival rate, decreased tumor burden, as well as enhanced tumor growth inhibition rate and apoptosis. The favoring effect was related to elevation of anti-tumor immunity which manifested as the increased anti-tumor cytokines (INF-γ, IL-17, IL-2 and IL-6). Further studies indicated the elevation was ascribed to ginsenosides promoted reproduction of gut probiotics including Akkermansia, Bifidobacterium and Lactobacillus. Moreover, co-administration of ginsenosides in mice alleviated CTX-induced gut mucositis, including lower gut permeability, less diarrhea, less epithelium damage and higher tight junction proteins. Further researches suggested the alleviation was related to ginsenosides activated Nrf2 and inhibited NFκB pathways. CONCLUSION: Ginsenosides show dual roles to facilitate the anti-tumor efficiency of CTX, namely promote the anti-tumor immunity through maintaining gut microflora and ameliorate gut mucositis by modulating Nrf2 and NFκB pathways.

Ginsenosides for the treatment of metabolic syndrome and cardiovascular diseases: Pharmacology and mechanisms.

Epidemiological studies showed that the metabolic syndromes (MetS) and cardiovascular diseases (CVDs) are responsible for a serious threat to human health worldwide. MetS is a syndromes characterized by fat metabolism disorder, obesity, diabetes, insulin resistance and other risk factors, which increases the risk of CVDs initiation and development. Although certain drugs play a role in lowering blood sugar and lipid, some side effects also occur. Considering the multiple pathogenesis, a great deal of natural products have been attempted to treat metabolic syndromes. Ginsenosides, as the active components isolated from Panax ginseng C.A.Mey, have been reported to have therapeutic effects on MetS and CVDs, of which pharmacological mechanisms were further studied as well. This review aims to systematically summarize current pharmacological effects of ginsenosides on MetS and CVDs, potential mechanisms and clinic trials, which will greatly contribute to the development of potential agents for related disease treatment.

Chemical constituents of Panax ginseng and Panax notoginseng explain why they differ in therapeutic efficacy.

Panax ginseng (Meyer) and Panax notoginseng (Burkill), belonging to the family Araliaceae, are used worldwide as medicinal and functional herbs. Numerous publications over the past decades have revealed that both P. notoginseng and P. ginseng contain important bioactive ingredients such as ginsenosides and exert multiple pharmacological effects on nervous system and immune diseases. However, based on traditional Chinese medicine (TCM) theory, their applications clearly differ as ginseng reinforces vital energy and notoginseng promotes blood circulation. In this article, we review the similarities and differences between ginseng and notoginseng in terms of their chemical composition and pharmacological effects. Their chemical comparisons indicate that ginseng contains more polysaccharides and amino acids, while notoginseng has more saponins, volatile oil, and polyacetylenes. Regarding pharmacological effects, ginseng exhibits better protective effects on cardiovascular disease, nerve disease, cancer, and diabetes mellitus, whereas notoginseng displays a superior protective effect on cerebrovascular disease. The evidence presented in this review facilitates further research and clinical applications of these two herbs, and exploration of the relationship between the chemical components and disease efficacy may be the critical next step.

YiQiFuMai Lyophilized Injection ameliorates tPA-induced hemorrhagic transformation by inhibiting cytoskeletal rearrangement associated with ROCK1 and NF-κB signaling pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Thrombolytic therapy with tissue plasminogen activator (tPA) after ischemic stroke exacerbates blood-brain barrier (BBB) breakdown and leads to hemorrhagic transformation (HT). YiQiFuMai Lyophilized Injection (YQFM) is a modern preparation derived from Sheng-mai San (a traditional Chinese medicine). YQFM attenuates the BBB dysfunction induced by cerebral ischemia-reperfusion injury. However, whether YQFM can suppress tPA-induced HT remains unknown. AIM OF THE STUDY: We investigated the therapeutic effect of YQFM on tPA-induced HT and explored the underlying mechanisms in vivo and in vitro to improve the safety of tPA use against stroke. METHODS: Male C57BL/6J mice were subjected to 45 min of ischemia and 24 h of reperfusion. tPA (10 mg/kg) were infused 2 h after occlusion and YQFM (0.671 g/kg) was injected 2.5 h after occlusion. The in vitro effect of YQFM (100, 200, 400 µg/mL) on tPA (60 µg/mL)-induced dysfunction of the microvascular endothelial barrier in the brain following oxygen-glucose deprivation/reoxygenation (OGD/R) was observed in bEnd.3 cells. RESULTS: YQFM suppressed tPA-induced high hemoglobin level in the brain, mortality, neurologic severity score, BBB permeability, expression and activation of matrix metalloproteinase (MMP)-9 and MMP-2, and degradation of tight-junction proteins. Furthermore, YQFM significantly blocked tPA-induced brain microvascular endothelial permeability and phosphorylation of Rho-associated kinase (ROCK)1, myosin light chain (MLC), cofilin and p65 in vivo and in vitro. CONCLUSION: YQFM suppressed tPA-induced HT by inhibiting cytoskeletal rearrangement linked with ROCK-cofilin/MLC pathways and inhibiting the nuclear factor-kappa B pathway to ameliorate BBB damage caused by tPA.

Effect of sulfur-fumigation process on ginseng: Metabolism and absorption evidences.

ETHNOPHARMACOLOGICAL RELEVANCE: Sulfur-fumigation has been developed to prevent insects and molds during post-harvest handling of Panax ginseng C.A. Mey (ginseng) in the near decades. Our previous study indicated sulfur-fumigation could transform ginsenosides, the active components of ginseng, into sulfur-containing derivatives (SFCDs), the artifacts with unknown toxicity. However, whether the biotransformation could be occurred and absorption characteristics between ginsenosides and SFCDs are still needed to further investigate. AIM OF THE STUDY: To evaluate the effect of sulfur-fumigation process on ginseng through comparing the metabolic profile and absorption characteristics between ginsenoside Rg1, Re and their SFCDs. MATERIALS AND METHODS: Intestinal microflora and liver S9 fraction were utilized to compare the metabolic profile, and single-pass intestinal perfusion and Caco-2 cell models were applied to compare the absorption characteristics, between Rg1, Re and their SFCDs. RESULTS: Rg1 and Re were metabolized to 7 none sulfur-containing metabolites, while their SFCDs were metabolized to 18 sulfur-containing metabolites. The intestinal absorption and transport of Rg1 and Re were much greater than their SFCDs. Besides, the uptakes of Rg1 and Re were transport-dependent, but their SFCDs were non-transport-dependent. CONCLUSION: Ginsenosides and their SFCDs could not be bio-transformed with each other and their absorption characteristics were quite different, which suggested that sulfur-fumigation is not a feasible post-harvest process of ginseng.

New insights into potential nutritional effects of dietary saponins in protecting against the development of obesity.

Excessive energy intake, poor physical exercise and genetics/epigenetics are instrumental for the development of obesity. Because of rapidly emerging evidences related to off-target effects and toxicity of anti-obesity drugs, there is a need to search for more effective and targeted drugs for treatment of obesity. Substantial studies have found the nutritional effects of dietary saponins (bio-detergents) in terms of decreasing the synthesis of lipids, suppressing adipogenesis, inhibiting intestinal absorption of lipids, and promoting fecal excretion of bile acids and triglycerides. Dietary saponin have been approved as potent pancreatic lipase inhibitors, disaccharidase enzyme inhibitors, antagonistic to in vitro lipogenesis and in vivo appetite suppressants, antioxidants, immune-regulators, prevent fatty liver formation, protects epithelial vasculature and regulate body weight. Many dietary saponins, such as sibutramine, morgoside, sessiloside, soysaponin B, and diosgenin, have treatment potential against the development of obesity. Excellent scientific achievements have been developed for a better understanding the mechanism of saponins in preventing obesity.

Shen-ling-bai-zhu-san, a spleen-tonifying Chinese herbal formula, alleviates lactose-induced chronic diarrhea in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Shen-ling-bai-zhu-san (SLBZS) was firstly documented in ancient Chinese medical works "Tai Ping Hui Min He Ji Ju Fang" in Song-dynasty. It has been widely used for treating gastrointestinal disorders such as diarrhea with poor appetite for about 900 years. The present study is to observe the effects of SLBZS on high lactose diet-induced chronic diarrhea. MATERIALS AND METHODS: Rats were subjected to a high lactose diet to induce chronic diarrhea, which were then administrated with SLBZS or smecta. General symptom, body weight, food consumption, water intake and fecal fluid content were recorded every day. The intestinal absorption function was determined by d-xylose uptake assay. The ultrastructures of intestine segments including jejunum, ileum, proximal and distal colon were observed by transmission electron microscopy. Additionally, sodium transport proteins including γ-epithelial sodium channel (ENAC-γ) and sodium/potassium-transporting ATPase subunit alpha-1 (ATP1A1) in distal colon were detected by immunohistochemistry and western blotting. RESULTS: Diarrheal rats produced watery or loose, sticky feces, and presented inactiveness and grouping. A high lactose diet caused a significant decline in body weight, serum d-xylose level as well as food consumption rather than water intake. In contrast, general symptoms were improved to a certain extent and body weight loss was alleviated in the rats treated by SLBZS for one week. Fecal fluid content in diarrheal rats treated by SLBZS presented a gradual decrease trend with about 55% in the end, which was significantly less than the model group with about 81%. Meanwhile, SLBZS significantly improved the serum d-xylose level and reversed abnormal changes of tight junctions and microvilli in intestine. Additionally, SLBZS significantly modulated the abnormal expressions of ENAC-γ and ATP1A1 in distal colon of diarrheal rats. CONCLUSIONS: These findings suggested that SLBZS exhibited ameliorating effects against lactose-induced diarrhea, which might be attributed to its modulations on intestinal absorption function as well as mucosal ultrastructure.

Quantitative proteomics reveal antidepressant potential protein targets of xiaochaihutang in corticosterone induced model of depression.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaochaihutang (XCHT), one of famous Chinese herbal prescription for treating Shaoyang symptom, has been used successfully in depressive disorders for many years. Our laboratory has demonstrated that XCHT remarkably alleviated various depressive behaviors induced by several depressive animal models, but previous studies only focused on one or several protein targets, lacked dynamic change and interrelation of proteins. Therefore, potential protein targets and mechanisms are required further systematic investigation. AIM OF THE STUDY: To discover and assess the differentially expressed proteins (DEPs) of hippocampus after oral administration of XCHT in corticosterone (CORT) induced model of depression by using isobaric tags for relative and absolute quantification (iTRAQ) analysis. MATERIALS AND METHODS: The antidepressant effects of XCHT were assessed by two behavioral despair models (forced swimming test and tail suspension test) in CORT induced model of depression. The DEPs of hippocampus after XCHT treatment were investigated by iTRAQ analysis. Potential protein targets and mechanisms were assessed by gene ontology (GO), Kyoto encyclopedia of gene and genomes (KEGG) and protein-protein interaction (PPI) network. RESULTS: Our data demonstrated XCHT could significantly improve depressive behaviors. A total of 241 DEPs were identified after XCHT treatment, including 68 up regulation and 173 down regulation proteins. GO enrichment results indicated that XCHT mainly regulated intracellular structural proteins involved in cellular response to stress, transferase activity and steroid hormone. KEGG enrichment analysis showed that endocytosis might be the principal pathway of XCHT on depression. PPI analysis predicted cell division cycle and apoptosis regulator protein 1 (Ccar1) and Calretinin (Calb2) might play the central roles in XCHT's antidepressant network. CONCLUSION: Our results indicate that XCHT plays the important roles in antidepressant action by restoring DEPs, which results in the dysregulation of hippocampal neurogenesis, neurotransmitter and steroid hormone. The current results wish to provide novel perspectives for revealing the potential protein targets of XCHT on depression.

Clinical efficacy and safety of Aidi injection plus paclitaxel-based chemotherapy for advanced non-small cell lung cancer: A meta-analysis of 31 randomized controlled trials following the PRISMA guidelines.

ETHNOPHARMACOLOGICAL RELEVANCE: As an important Chinese herb injection, Aidi injection is composed of the extracts from Astragalus, Eleutherococcus senticosus, Ginseng, and Cantharis. Aidi injection plus paclitaxel-based chemotherapy is often used to in the treatment of non-small cell lung cancer (NSCLC) in China. AIM OF THE STUDY: The objective of this study is to further confirm whether Aidi injection can improve the tumor responses and survivals, and reveal its safety, optimal usage and combination with paclitaxel. MATERIALS AND METHODS: A meta-analysis was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. All randomized controlled trials (RCTs) concerning the Aidi injection plus paclitaxel-based chemotherapy for NSCLC were selected. Main outcomes were objective response rate (ORR), disease control rate (DCR), survivals, quality of life (QOL) and adverse drug reactions (ADRs). All data were extracted by using a standard data extraction form and synthesized through meta-analysis. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used for rating the quality of evidence. RESULTS: Thirty-one RCTs involving 2058 patients were included, and most trials had an unclear methodological bias risk. The risk ratio (RR) and 95% confidence intervals (CI) of ORR, DCR, QOL, neutropenia, thrombocytopenia, gastrointestinal toxicity and liver injury were as following: 1.32 (1.20-1.46), 1.14 (1.09-1.20), 1.89 (1.66-2.16), 0.61 (0.51-0.74), 0.62 (0.45-0.87), 0.59 (0.49-0.72) and 0.52 (0.36-0.75). Compared to chemotherapy alone, all differences were statistically significant. Subgroup analysis showed that only with the TP, Aidi injection could increase the ORR and DCR. Treatment with 100 ml, 80 ml or 50 ml/time, and 14 days/2 cycles or 21 days/2-4 cycles, Aidi injection could increase the ORR and DCR, respectively. Sensitivity analysis showed that the results had good robustness. None of the trials reported the overall survivals (OS), progression free survival (PFS). The quality of evidences was moderate. CONCLUSIONS: Current moderate evidence revealed that Aidi injection plus paclitaxel-based chemotherapy, especially TP can significantly improve the clinical efficacy and QOL for patients with stage III/IV NSCLC. Aidi injection can relieve the risk of hematotoxicity, gastrointestinal toxicity and liver injury in patient with NSCLC receiving paclitaxel-based chemotherapy. The optimal usage may be 50 ml/time and 14 days/2 cycles.

Aidi injection plus platinum-based chemotherapy for stage IIIB/IV non-small cell lung cancer: A meta-analysis of 42 RCTs following the PRISMA guidelines.

ETHNOPHARMACOLOGICAL RELEVANCE: Aidi injection is one of the most commonly used Chinese patent medicines for advanced non-small cell lung cancer (NSCLC). It is made from an extraction of Mylabris Phalerata, Radix Astragalus, Radix Ginseng, and Acanthopanax Senticosus. AIM OF THE STUDY: The objective of this study is to evaluate the efficacy and safety of Aidi injection in combination with platinum-based chemotherapy for stage IIIB/IV NSCLC. MATERIALS AND METHODS: A systematic review and meta-analysis were performed following the PRISMA (the Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Trials were combined using Review Manager 5.3 and Comprehensive Meta-Analysis(CMA) 2.0. Dichotomous data were expressed as risk ratio (RR) and continuous outcomes as weighted mean difference (WMD), with their 95% confidence intervals (CI) respectively. All randomized controlled trials (RCTs) comparing Aidi injection plus platinum-based chemotherapy versus platinum-based chemotherapy, with efficacy and safety outcomes were selected. Disease Control Rate (DCR) was the primary outcome, Objective Response Rate (ORR), survival rate, quality of life (QOL), and toxic effects were the secondary outcomes. RESULTS: 42 RCTs recruiting 4081 patients with stage IIIB/IV NSCLC were included, with overall low-moderate methodological quality. Compared with platinum-based chemotherapy alone, Aidi injection plus platinum-based chemotherapy can increase relative benefit of DCR (RR = 1.13, 95% CI 1.09-1.16, P < 0.00001), ORR (RR = 1.26, 95% CI 1.18-1.36, P < 0.00001), improve 1-, 2-, 3-year survival rates (RR = 1.14, 95% CI 1.02-1.28, P = 0.03; RR = 1.31, 95% CI 1.05-1.64, P = 0.02; and RR = 1.88, 95% CI 1.32-2.67, P = 0.0005, respectively), QOL (RR = 1.80, 95% CI 1.61-2.01, P < 0.00001), and reduce severe (grade 3 and 4) toxicities by 36% (RR = 0.64, 95% CI 0.58-0.70, P < 0.00001). CONCLUSIONS: From the available evidence, compared with platinum-based chemotherapy alone, Aidi injection plus platinum-based chemotherapy improves the clinical efficacy and alleviates the toxicity of chemotherapy in patients with stage IIIB/IV NSCLC. However, considering the intrinsic limitations of the included RCTs, well-designed, rigorously performed, high-quality trials are still required to further assess and confirm the results.