The potential therapeutic effects of Panax notoginseng in osteoporosis: A comprehensive review.

Background: Fructus Ligustri Lucidi (FLL) has now attracted increasing attention as an alternative medicine in the prevention and treatment of osteoporosis. This study aimed to provide a general review of traditional interpretation of the actions of FLL in osteoporosis, main phytochemical constituents, pharmacokinetics, pharmacology in bone improving effect, and safety. Materials and Methods: Several databases, including PubMed, China National Knowledge Infrastructure, National Science and Technology Library, China Science and Technology Journal Database, and Web of Science were consulted to locate publications pertaining to FLL. The initial inquiry was conducted for the presence of the following keywords combinations in the abstracts: Fructus Ligustri Lucidi, osteoporosis, phytochemistry, pharmacokinetics, pharmacology, osteoblasts, osteoclasts, salidroside. About 150 research papers and reviews were consulted. Results: FLL is assumed to exhibit anti-osteoporotic effects by improving liver and kidney deficiencies and reducing lower back soreness in Traditional Chinese Medicine (TCM). The data from animal and cell experiments demonstrate that FLL is able to improve bone metabolism and bone quality in ovariectomized, growing, aged and diabetic rats through the regulation of PTH/FGF-23/1,25-(OH)2D3/CaSR, Nox4/ROS/NF-κB, and OPG/RANKL/cathepsin K signaling pathways. More than 100 individual compounds have been isolated from this plant. Oleanolic acid, ursolic acid, salidroside, and nuzhenide have been reported to exhibit the anti-osteoporosis effect. The pharmacokinetics data reveals that salidroside is one of the active constituents, and that tyrosol is hard to detect under physiological conditions. Acute and subacute toxicity studies show that FLL is well tolerated and presents no safety concerns. Conclusions: FLL provides a new option for the prevention and treatment of osteoporosis, which attracts rising interests in identifying potential anti-osteoporotic compounds and fractions from this plant. Further scientific evidences are expected from well-designed clinical trials on its bone protective effects and safety.

Objective This meta-analysis evaluated the curative effect of the compatibility of Astragalus membranaceus and Panax notoginseng (ARPN) as main components on diabetic nephropathy. Methods We used various Chinese and English databases, including the Cochrane Library, PubMed, Embase, Web of Science, the China National Knowledge Infrastructure (CNKI), China Biology Medicine Disc (SinoMed), VIP, and Wanfang, to search for randomized controlled trials on the compatibility of Astragalus membranaceus and Panax notoginseng as main components. After data extraction, meta-analysis was performed with Review Manager 5.4.0 and Stata 15, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) framework was used to evaluate the quality of the evidence. Result A total of 17 studies involving 1342 patients with diabetic nephropathy were included. Compared with the control group, ARPN can significantly improve the clinical effective rate of diabetic nephropathy (OR 5.12, 95% CI 3.42 to 7.66, P < 0.00001), and the curative effect of reducing UAER (MD −26.67, 95% CI −31.30 to −22.04, P < 0.00001) and 24 h urinary protein (SMD −0.58, 95% CI −0.75 to −0.41, P < 0.00001) is also significantly better than that of the control group, and it can also improve the renal function(Scr: MD −13.78, 95% CI −25.39 to −2.17, P=0.02; BUN: MD −0.74, 95% CI −1.27 to −0.20, P=0.007). In addition, it can also reduce glycosylated hemoglobin (SMD −1.30, 95% CI −2.33 to −0.27, P=0.01) and blood lipid(TC: SMD −0.62, 95% CI −0.95 to −0.29, P=0.0002; TG: SMD −0.47, 95% CI −0.75 to −0.19, P=0.0009; LDL: SMD −0.43, 95% CI −0.68 to −0.18, P=0.0008), and improve the TCM syndrome score (MD −4.87, 95% CI −6.17 to −3.57, P < 0.00001). Subgroup analysis suggested that the treatment plan of the control group could be the sources of heterogeneity. All the included studies had no obvious adverse effects. Conclusions The compatibility of Radix Astragali and Radix notoginseng as the main components can effectively improve the renal function of patients with diabetic nephropathy and delay the progress of diabetic nephropathy. However, the results of this study need further research to be confirmed because of the uncertainty of the evidence and the suboptimal risk bias.

Cnidii Fructus: A traditional Chinese medicine herb and source of antiosteoporotic drugs

Gut microbiota: A new key of understanding for Panax notoginseng against multiple disorders and biotransformation.

Context Panax notoginseng (Burk.) F.H. Chen (Araliaceae) preparations (PNP) are traditional Chinese medicines used as adjuvant therapeutics for diabetic kidney disease (DKD). Objective To systematically review the efficacy of PNP as adjunct DKD therapy, including their effects on kidney function, serum lipid levels and fasting blood glucose levels. Methods The databases PubMed, Embase, Medline, Cochrane Library, CINAHL, China Biology Medicine disc, Wanfang, VIP and China National Knowledge Infrastructure were systematically searched from the date of their inception until May 2019. Panax notoginseng, Panax notoginseng saponins, Lulutong, Xueshuantong and Xuesaitong were the key terms searched. Randomized controlled trials (RCTs) comparing the combined use of PNP and conventional medicines (CM) versus CM for DKD were included. Data were pooled using random or fixed effect models depending on heterogeneity. Results In total, 24 RCTs involving 1918 participants were analysed. Adjunct PNP with CM was associated with reduction of albuminuria (MD –26.89 mg, 95% CI: –33.35 to –20.42), proteinuria (MD –0.32 g/24 h, 95% CI: –0.36 to –0.27), serum creatinine (MD –4.52 μmol/L, 95% CI: –8.71 to –0.32), total cholesterol (MD –1.56 mmol/L, 95% CI: –2.33 to –0.78), triglycerides (TG) (MD –0.56 mmol/L, 95% CI: –0.80 to –0.31) and low-density lipoprotein cholesterol (MD –0.94 mmol/L, 95% CI: –1.49 to –0.40) compared with CM. Conclusions This is the first meta-analysis investigating adjuvant PNP therapy for DKD. PNP apparently exerted beneficial effects on kidney function and improved the metabolism of serum lipids by CM. Further, well-conducted, high-quality trials on DKD patients are needed to provide high-quality evidence.

BackgroundDiabetic nephropathy (DN) is a major microvascular complication of diabetes and constitutes a leading cause of end-stage renal disease (ESRD). Panax notoginseng is a widely utilized traditional Chinese medicinal herb with diverse pharmacological properties, including antioxidant, antithrombotic, and glucolipid metabolism-regulating activities. Preclinical studies have demonstrated the renoprotective effects of Panax notoginseng in DN animal models. However, a comprehensive meta-analysis of these studies is currently lacking, and the dose-time-response relationship remains unexplored.ObjectiveThis study aimed to systematically evaluate the efficacy of Panax notoginseng in animal models of DN and, for the first time, to explore its dose-time-response relationship. Additionally, we sought to summarize the potential mechanisms underlying its therapeutic effects on DN.MethodsA systematic search was conducted across seven databases: PubMed, Web of Science, Embase, Chinese Biomedical Database (CBM), CNKI, WanFang, and VIP. The methodological quality of the included studies was assessed using SYRCLE’s risk of bias tool. Statistical analyses were performed using STATA 14.0 software. Primary outcomes included fasting blood glucose (FBG), serum creatinine (SCr), blood urea nitrogen (BUN), 24-h urinary protein (24 h UPro), and kidney index (KI). Secondary outcomes encompassed indicators related to inflammatory response, oxidative stress, glucose and lipid metabolism, and fibrosis. Where substantial heterogeneity was present, sensitivity and subgroup analyses were conducted to explore its sources. Publication bias was assessed via Egger’s test and funnel plots. The dose-time-response relationship of Panax notoginseng for DN was evaluated using a three-dimensional surface plot analysis.ResultsA total of 37 studies were included in the final meta-analysis. The results demonstrated that Panax notoginseng significantly ameliorated FBG, SCr, BUN, 24 h UPro, and KI levels. Furthermore, Panax notoginseng significantly modulated key inflammatory markers, including interleukin-1β (IL-1β), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), and monocyte chemoattractant protein-1 (MCP-1). It also altered oxidative stress markers, such as superoxide dismutase (SOD) and malondialdehyde (MDA). In addition, Panax notoginseng exerted beneficial effects on lipid metabolism, as evidenced by reduced levels of total cholesterol (TC) and triglycerides (TG). It also attenuated the expression of the pro-fibrotic marker transforming growth factor-β1 (TGF-β1). The three-dimensional dose-time-response analysis revealed that treatment with PNS at a dosage of 20–200 mg/kg/d for 8–12 weeks conferred optimal therapeutic benefits in the DN models.ConclusionPanax notoginseng may delay the progression of DN through multiple pathways, including anti-inflammatory, antioxidant, glucolipid metabolism-regulating, and anti-fibrotic mechanisms. However, further studies are still needed to verify its efficacy and mechanisms.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/view/CRD420250653856.

ObjectiveThis study aims to investigate the effect of exosomes derived from Panax notoginseng on the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) and to elucidate the underlying intracellular signaling mechanisms.MethodsExosomes from Panax notoginseng were isolated using differential centrifugation combined with sucrose density gradient centrifugation. The morphology of the exosomes was characterized by transmission electron microscopy (TEM), while size distribution and concentration were determined via nanoparticle tracking analysis (NTA). rBMSCs were isolated and identified by flow cytometry, and the uptake of fluorescently labeled Panax notoginseng exosomes by rBMSCs was confirmed using confocal microscopy. The optimal concentration of exosomes was determined using the CCK-8 assay. Osteogenic differentiation was evaluated by measuring alkaline phosphatase (ALP) activity, performing ALP staining, and conducting Alizarin Red S staining. The expression levels of osteogenic markers (collagen type I(COL1), ALP, osteopontin (OPN), and Runt-related transcription factor 2 (RUNX2)) were quantified at the mRNA (RT-qPCR) and protein (Westem blotting)levels. High-throughput RNA sequencing and bioinformatics analyses (Gene Ontology (GO),Kyoto Encyclopedia of Genes and Genomes (KEGG)) were employed to identify differentially expressed genes and enriched pathways. Key pathways were validated using specific inhibitors.ResultsExosomes derived from Panax notoginseng promote the osteogenic differentiation of rBMSCs through the activation of the PI3K/AKT signaling pathway. This study provides experimental evidence and theoretical support for the application of herbal exosomes in bone tissue engineering and the treatment of osteoporosis.ConclusionPanax notoginseng exosomes promote osteogenic differentiation of rBMSCs by activating the PI3K/AKT pathway, providing experimental evidence and theoretical support for the application of herbal exosomes in bone tissue engineering and osteoporosis treatment.

Panax notoginseng is a traditional Chinese medicine containing various constituents, including the saponins, polysaccharides, polyacetylenes, amino acids, etc. It has beneficial functions, such as the anti-inflammatory, antitumor, hepatoprotective, and anti-aging effects. Among these, P. notoginseng polysaccharides (PNPs) have been exploited because of their extensive pharmacological effects, being ranked as one of the current research hotspots, especially for the functional foods and medical practice. In this review, the literature related to PNPs in the past 20 years was surveyed and analyzed using both the China National Knowledge Infrastructure (CNKI) and Web of Science (WOS) databases. The visualization diagram shows that current studies on PNPs mainly focus on the antioxidant and immunomodulatory activities and structural characterization. In addition, the extraction, separation, purification, chemical analysis, structural characteristics, bioactivities, and applications of PNPs are outlined, in detail, aimed to provide valuable information for the further study, development, and utilization regarding PNPs.

Comparative effectiveness of Panax notoginseng saponins-related agents and antiplatelet agents in ischemic stroke: A systematic review and network meta-analysis.

ObjectiveTo evaluate the efficacy and safety of combined traditional Chinese medicine in the adjuvant treatment of proliferative diabetic retinopathy (PDR) by Meta-analysis.MethodsPubMed, Embase, Web of Science, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang databases were searched by computer. Random controlled clinical trials (RCTS) using traditional Chinese medicine as adjuvant therapy for proliferative diabetic retinopathy were screened, and Stata16.0 software was used to perform meta-analysis on the final included literatures.ResultsA total of 18 studies involving 1392 patients were included. Meta-analysis showed that the clinical effective rate OR=2.99 (CI: 2.18-4.10, I2 = 42.7%, P<0.05); Visual acuity MD=0.10(CI: 0.06-0.13, I2 = 0%, P<0.05); Fundus efficacy OR=5.47 (CI: 1.33-22.51, I2 = 71.4%, P<0.05); Neovascularisation regression rate OR=8 (CI: 3.83-16.71, I2 = 30.1%, P<0.05); Macular foveal thickness MD=-44.24 (CI: -84.55–3.93, I2 = 95.6%, P<0.05); Absorption of vitreous hemorrhage OR=4.7 (CI: 2.26-9.77, I2 = 0%, P<0.05); Fasting blood glucose MD=-0.23, (CI: -0.38–0.07, I2 = 0%, P<0.05); 2h postprandial blood glucose MD=-0.19 (CI: -0.52-0.14, I2 = 0%, P=0.25). From the results, the combined Chinese medicine adjuvant therapy showed better efficacy than the control group. A total of 69 kinds of traditional Chinese medicine were involved in 18 studies, among which the top four applied frequencies were Panax notoginseng, Rehmannia rehmannii, Astragalus membranaceus and Poria cocos. Most of the medicines were sweet and bitter in taste, the qi tended to be slight cold and cold, and the meridian tropism belongs to the liver meridian.ConclusionThe combination of traditional Chinese medicine adjuvant therapy has a good curative effect on PDR patients. However, the relevant clinical trials are few and more high-quality clinical trials are still needed, what’s more the attention should be paid to the exploration of its safety.

The characteristics of scoliosis afflicting school children and adolescents in mainland China are still unclear. Therefore, we conducted a systematic review to estimate scoliosis's prevalence and characterise its distribution in China. We screened PubMed, Scopus, WanFang, China National Knowledge Infrastructure, National Science and Technology Library, and WeiPu databases for mainland China articles published between 1 January 1980 and 31 October 2022. Among them, we identified population-wide scoliosis studies in school children and adolescents. The main outcomes were the positive rate of primary screening and the prevalence of final screening. Primary screening mainly included general examination with/without the forward bending test in school. The final screening entailed clinical diagnosis by Röntgen radiation in a hospital (based on primary screening). A meta-analysis of scoliosis distribution by gender was performed to calculate the odds ratios (ORs) and 95% confidence intervals (CIs). Further, we analysed the distributions of scoliosis by age, region, aetiological type, and severity of curvature, in addition to the correlation between its prevalence and altitude or latitude. 77 studies with 2 224 320 participants were included. The positive rate through primary screening was 3.97%, whereas the prevalence of scoliosis at final screening was 1.20%. Analysing the data revealed a higher prevalence of scoliosis in girls (OR = 1.57; 95% CI = 1.38-1.81). The age-wise peak rate of scoliosis was 15-16 years (1.07%) in boys and 13-14 years (1.42%) in girls. The mean prevalence of scoliosis was 1.07% in the western region, 1.54% in the central, and 1.35% in the eastern. Scoliosis prevalence was not correlated with either altitude or latitude. The prevalence of idiopathic and congenital scoliosis was 1.18 and 0.03%. Among all subjects with scoliosis, 79.10 and 16.80% had mild and medium disease severity. According to this comprehensive study using data sets of scoliosis in adolescents across mainland China, the mean prevalence of scoliosis is 1.20%, yet 1.57 times higher in girls than boys, and is most prevalent in the middle region. Overall, scoliosis in adolescents could pose a burden to public health in mainland China. PROSPERO CRD42021231987.

Salvia miltiorrhiza in diabetes: A review of its pharmacology, phytochemistry, and safety

Herb-drug interactions between Panax notoginseng or its biologically active compounds and therapeutic drugs: A comprehensive pharmacodynamic and pharmacokinetic review.

Notoginsenoside R1 is one of major bioactive compounds extracted from Panax notoginseng (Burk.) dry roots and rhizomes of F.H. Chen, which has been increasingly used for enhancing cognition and physical health worldwide. The objective of this study was to review the pharmacological effects of notoginsenoside R1 in a systematic manner. We performed searches on databases including MEDLINE (Pubmed), Google Scholar and Web of Science, the System for Information on to select the original research publications reporting the biological and pharmacological effects of notoginsenoside R1 from in vitro and in vivo studies regardless of publication language and study design. Notoginsenoside R1 exhibited potent characteristics of neuroprotective, anti-inflammatory, anti-apoptosis and anti-ischemia-reperfusion injury properties etc. The cytotoxic effects of notoginsenoside R1 were dependent on different types of cell lines. Other pharmacological effects including accumulation of lipopolysac chaired-induced microcirculation, endothelial injury, hypoxia-reoxygenation injury effects have been mentioned, but the results were considerably diverged. A higher quality of evidence on clinical trial studies is highly recommended to confirm the efficacy of notoginsenoside R1.

Objective: This systematic review aimed to evaluate the nephroprotective effect of Panax notoginseng.Methods: The search for scientific articles in the literature was carried out in the Medline (PubMed), Web of Science, Embase, and Virtual Health Library (BVS) databases. Eligibility criteria consisted of preclinical in vivo or clinical studies that demonstrated the nephroprotective effect of Panax notoginseng, as assessed by one or more of the following laboratory tests: serum creatinine, serum urea, glomerular filtration rate, creatinine clearance, proteinuria, or albuminuria. Results: Fourteen articles were included, all of which consisted of preclinical trials. The nephropathy models used in the studies were diabetic kidney disease (n=8), kidney injury induced by nephrotoxic substances (n=5), or ischemia (n=1). All studies showed that Panax notoginseng has a nephroprotective effect when used in the treatment of kidney diseases. Although three studies did not observe a reduction in serum creatinine and/or urea levels, these studies found that albuminuria decreased significantly. Conclusion: Panax notoginseng has a nephroprotective effect in different animal models of nephropathy. The clinical use of Panax notoginseng tends to be promising as an adjuvant in the pharmacotherapy of renal dysfunctions and in the prevention of drug-induced nephrotoxicity.