Panax ginseng C. A. Meyer is a medicinal and edible plant traditionally used for cardioprotection and has been shown to exert protective effects against doxorubicin-induced cardiotoxicity (DIC). However, the role and underlying mechanism of ginseng acidic polysaccharides (GAP) remain unclear. Here, the cardioprotective effects of GAP were evaluated in H9C2 cell and a chronic DIC mouse model, combined with 16S rRNA sequencing and metabolomics. The results showed that GAP exhibited molecular weights of 5916 and 2488 Da, with galacturonic acid as the main monosaccharide component. In vitro experiments confirmed that GAP protected H9C2 cells from DOX-induced injury by mitigating oxidative stress, stabilizing mitochondrial membrane potential, and inhibiting apoptosis. In vivo, GAP significantly improved left ventricular ejection fraction and fractional shortening in mice with DIC, reduced myocardial injury markers, and alleviated myocardial fibrosis, hypertrophy, and apoptosis. Additionally, GAP ameliorated DOX-induced gut microbial dysbiosis by enriching beneficial bacteria (norank_Muribaculaceae), upregulated intestinal barrier proteins, and increased fecal SCFA levels. Serum metabolomics showed that GAP restored arginine metabolic homeostasis by downregulating ASS1, ARG2, and iNOS in myocardial tissues. The multi-omics integration analysis revealed a significantly negative correlation between norank_Muribaculaceae and the levels of arginine, ornithine and citrulline in the arginine metabolic pathway. Furthermore, GAP activated the Nrf2/HO-1 pathway, and inhibited cardiomyocyte apoptosis by regulating BAX/BCL-2 expression. This study shows that GAP protects against DIC by regulating the norank_Muribaculaceae-arginine metabolism-Nrf2/HO-1 axis, offering experimental evidence to support its future clinical translational research.

Acute cold exposure/rewarming (ACE/R) disrupts cardiovascular homeostasis and causes severe myocardial injury, yet effective countermeasures are scarce. Ginger-processed American ginseng (GPAG), a medicine-food homologous herb, exerts anti-inflammatory, antioxidant, and metabolic-regulatory effects; however, its cardioprotective mechanisms against ACE/R remain unclear. An ACE/R rat model was established by exposing rats to -15 °C for 6 h followed by 24 °C rewarming for 12 h, with 7-day GPAG gavage (1 and 2 g/kg) prior to cold exposure. Integrated multiomics, fecal microbiota transplantation (FMT), and fecal metabolite-cardiomyocyte intervention assays were employed to elucidate the gut-heart axis mechanism. GPAG ameliorated hemorheological disorders, restored cardiac dysfunction, and attenuated myocardial lesions. Mechanistically, GPAG remodels gut microbiota to generate functional metabolites that activate the myocardial AMPK/PGC-1α/PPARα pathway via the gut-heart axis, thereby optimizing cardiac energy metabolism and restoring mitochondrial homeostasis to alleviate ACE/R-triggered myocardial damage.

Panax ginseng C. A. Meyer is a medicinal and edible plant traditionally used for cardioprotection and has been shown to exert protective effects against doxorubicin-induced cardiotoxicity (DIC). However, the role and underlying mechanism of ginseng acidic polysaccharides (GAP) remain unclear. Here, the cardioprotective effects of GAP were evaluated in H9C2 cell and a chronic DIC mouse model, combined with 16S rRNA sequencing and metabolomics. The results showed that GAP exhibited molecular weights of 5916 and 2488 Da, with galacturonic acid as the main monosaccharide component. In vitro experiments confirmed that GAP protected H9C2 cells from DOX-induced injury by mitigating oxidative stress, stabilizing mitochondrial membrane potential, and inhibiting apoptosis. In vivo, GAP significantly improved left ventricular ejection fraction and fractional shortening in mice with DIC, reduced myocardial injury markers, and alleviated myocardial fibrosis, hypertrophy, and apoptosis. Additionally, GAP ameliorated DOX-induced gut microbial dysbiosis by enriching norank_Muribaculaceae, upregulated intestinal barrier proteins, and increased fecal SCFA levels. Serum metabolomics showed that GAP restored arginine metabolic homeostasis by downregulating ASS1, ARG2, and iNOS in myocardial tissues. The multi-omics integration analysis revealed a significantly negative correlation between norank_Muribaculaceae and the levels of arginine, ornithine and citrulline in the arginine metabolic pathway. Furthermore, GAP activated the Nrf2/HO-1 pathway, and inhibited cardiomyocyte apoptosis by regulating BAX/ BCL-2 expression. This study shows that GAP against DIC by regulating the gut microbiota, arginine metabolism and the Nrf2/HO-1 pathway, offering experimental evidence to support its future clinical translational research.

ABSTRACTThe sedative and hypnotic properties of 5,7,3′,4′,5′‐pentamethoxyflavone (PMF), a monomer extracted from the leaves of Murraya paniculata (L.) Jack, have been reported. However, the role of PMFs in the development of anxiety remains uncertain. An anxiety model was developed using chronic unpredictable mild stimulation (CUMS). Kunming mice were randomly allocated to the following groups: control, CUMS, PMF (50 mg/kg), PMF (100 mg/kg), and diazepam (3 mg/kg). The anxiolytic effects of PMFs were evaluated using elevated plus maze (EPM) test and open field test (OFT). Enzyme‐linked immunosorbent assay (ELISA) kits were used to analyze the serum levels of corticosterone (CORT), 5‐hydroxytryptamine (5‐HT), gamma‐aminobutyric acid (GABA), and cyclic adenosine monophosphate (cAMP) in the hippocampus. High‐throughput‐16S rRNA sequencing was performed to investigate its effect on the composition of the gut microbiota. Subsequently, western blotting was performed to assess the expression of GABAergic synaptic‐associated proteins. PMF effectively mitigated CUMS‐induced anxiety‐like behavior. Further examination revealed that PMF treatment ameliorated dysfunction of the hypothalamic–pituitary–adrenal (HPA) axis and increased 5‐HT and GABA levels in the hippocampus. Notably, the ability of PMF to maintain the stability of GABAergic synapses by enhancing the species composition of the gut microbiota and acting on the adenosine a2a receptor (A2AR)/gephyrin/gamma‐aminobutyric acid A receptor alpha 2 (GABRA2) pathway revealed a previously unrecognized mechanism for the anxiolytic effect of PMF. These findings suggest that PMF enhances the expression of A2AR, preserves GABAergic synaptic stability, and reduces anxiety by modulating the microbiota composition. Thus, it holds promise as an anxiolytic agent.

AIM:Animals exhibit physiological changes designed to eliminate the perceived danger, provoking similar symptoms of fever. However, a high-grade fever indicates poor clinical outcomes. Caspase11 (Casp11) is involved in many inflammatory diseases. Whether Casp11 leads to fever remains unclear. In this study, we investigate the role of the preoptic area of the hypothalamus (PO/AH) microglia Casp11 in fever. METHODS:We perform experiments using a rat model of LPS-induced fever. We measure body temperature and explore the functions of peripheral macrophages and PO/AH microglia in fever signaling by ELISA, immunohistochemistry, immunofluorescence, flow cytometry, macrophage depletion, protein blotting, and RNA-seq. Then, the effects of macrophages on microglia in a hyperthermic environment are observed in vitro. Finally, adeno-associated viruses are used to knockdown or overexpress microglia Casp11 in PO/AH to determine the role of Casp11 in fever. RESULTS:We find peripheral macrophages and PO/AH microglia play important roles in the process of fever, which is proved by macrophage and microglia depletion. By RNA-seq analysis, we find Casp11 expression in PO/AH is significantly increased during fever. Co-culture and conditioned-culture simulate the induction of microglia Casp11 activation by macrophages in a non-contact manner. Microglia Casp11 knockdown decreases body temperature, pyrogenic factors, and inflammasome, and vice versa. CONCLUSION:We report that Casp11 drives fever. Mechanistically, peripheral macrophages transmit immune signals via cytokines to microglia in PO/AH, which activate the Casp11 non-canonical inflammasome. Our findings identify a novel player, the microglia Casp11, in the control of fever, providing an explanation for the transmission and amplification of fever immune signaling.

目的 观察人参多糖联合槲皮素对DSS诱导小鼠溃疡性结肠炎的保护作用.方法 50 只雄性Balb/c小鼠随机分为对照(Con)组,模型(DSS)组,人参多糖(GPS)联合槲皮素(QT)低、高剂量组及阳性药柳氮磺吡啶(SASP)组,每组 10 只.除对照组外,各组小鼠自由饮用3%葡聚糖硫酸钠(DSS)造模,GPS+QT低、高剂量组分别灌胃GPS+QT 50+50、100+100 mg/kg,SASP组灌胃SASP 500 mg/kg,Con组与DSS组灌胃等量0.5%羧甲基纤维素钠,灌胃体积均为 20 mL/kg,每天2次,连续7天.于造模7天后腹腔注射戊巴比妥钠30 mg/kg麻醉,处死小鼠,取结肠组织HE染色观察结肠病理变化;ELISA试剂盒检测结肠组织白细胞介素-1β(IL-1β)、白细胞介素-6(IL-6)、白细胞介素-18(IL-18)、干扰素-γ(IFN-γ)和肿瘤坏死因子-α(TNF-α)含量;生化试剂盒检测结肠组织超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-px)、过氧化氢酶(CAT)活性及丙二醛(MDA)含量.结果 HE染色显示,Con组隐窝结构完整清晰,DSS组炎症细胞浸润增加,隐窝扭曲并存在组织深度损伤,部分小鼠结肠出现侵蚀和溃疡,GPS+QT低、高剂量组和SASP组小鼠结肠浸润性炎症细胞明显减少,隐窝结构均较完整.ELISA结果显示,与Con组比较,DSS组小鼠结肠组织IL-6、IL-1β、IL-18、IFN-γ和TNF-α含量显著升高(P<0.01),与DSS组比较,GPS+QT低、高剂量组及SASP组各细胞因子含量均明显降低(P<0.05或P<0.01).生化试剂盒结果显示,DSS组小鼠结肠组织GSH-px、SOD和CAT活性显著降低(P<0.01),MDA含量显著升高(P<0.01),与DSS组比较,GPS+QT低、高剂量组及SASP组小鼠结肠组织SOD、GSH-px和CAT的活性显著升高(P<0.05或P<0.01),MDA的含量显著降低(P<0.05或P<0.01).结论 人参多糖联合槲皮素对DSS诱导小鼠溃疡性结肠炎具有保护作用,可能通过降低炎性因子表达,增强抗氧化酶活性,减轻自由基对心肌的氧化损伤来实现.

Myocardial ischemia-reperfusion (MI/R) injury occurs when coronary blood supply is impaired and then reestablished, leading to additional injury to the myocardial tissue, including mitochondria oxidative stress and apoptosis. Ginsenoside Rc is one of the main protopanaxadiol-type saponins, and there has been relatively little research on it. Despite research confirming that ginsenoside Rc regulates mitochondrial functions, its potential benefits against MI/R injury have not been explored. In this study, we examined the protective effects of ginsenoside Rc in MI/R injury, along with its underlying mechanisms, using an in vitro H9c2 cell model of oxygen-glucose deprivation/reoxygenation (OGD/R) and an in vivo rat model of MI/R injury. Prior to this, the H9c2 cells or rats were exposed to ginsenoside Rc with or without SIRT1 small interfering RNA (siRNA) or the selective SIRT1 inhibitor EX527. The results showed that after MI/R (or OGD/R) injury, ginsenoside Rc had a cardioprotective effect; improved cardiac function (or cell survival); reduced myocardial infarct size; decreased levels of creatine kinase-MB, cardiac troponin I, and lactate dehydrogenase (LDH) in the serum (or LDH release into culture medium); reduced cardiomyocyte apoptosis; and attenuated mitochondrial oxidative damage. Ginsenoside Rc pre-treatment also upregulated the anti-apoptotic protein Bcl-2 while downregulating the pro-apoptotic proteins Bax and cleaved caspase-3. Furthermore, the cardioprotective effect of ginsenoside Rc was concomitant with upregulated SIRT1 expression and downregulated Ac-FOXO1 expression. SIRT1 siRNA or SIRT1 inhibitor EX527 abolished the cardioprotective effects of ginsenoside Rc by inhibiting the SIRT1 signaling pathway. In conclusion, our findings demonstrate that ginsenoside Rc ameliorated MI/R injury by reducing mitochondrial oxidative stress and apoptosis, at least in part, by activating SIRT1.

Carbon tetrachloride (CCl4)-induced lipid peroxidation associated with hepatic oxidative stress and cell death is an important mechanism of acute liver injury (ALI). Ginsenoside Rd is considered an active ingredient of ginseng. Evidence suggests that ginsenoside Rd may improve ischaemic stroke, nerve damage, cancer and other diseases involving apoptosis, inflammation, oxidative stress, mitochondrial injury and autophagy. However, the effects of ginsenoside Rd on CCl4-induced ALI and its underlying mechanisms are still unclear. In this study, 0.25% CCl4 was injected intraperitoneally in mice to establish a CCl4-induced ALI model. In the Rd treatment group, Rd (10, 20[Formula: see text]mg/kg) doses were injected intraperitoneally 1[Formula: see text]h before and 23[Formula: see text]h after CCl4 administration. Ferroptosis inducer imidazole ketone erastin (IKE) was injected intraperitoneally 4[Formula: see text]h before CCl4 administration to explore the mechanism. The blood and liver were collected 24[Formula: see text]h after CCl4 administration to investigate the effect and mechanism of ginsenoside Rd on CCl4-induced ALI. Our results showed that ginsenoside Rd inhibited CCl4-induced ALI in mice. Ginsenoside Rd also downregulated CCl4-induced serum and liver iron, 4-hydroxynonenal, and 8-hydroxy-2 deoxyguanosine levels. Furthermore, it upregulated glutathione and glutathione peroxidase 4 levels. In addition, ginsenoside Rd downregulated the expression of cGAS and STING. Subsequently, the ferroptosis inducer imidazole ketone erastin significantly reversed the hepatoprotective effect and influence of ginsenoside Rd with regard to the indicators mentioned above. Our study confirmed that ginsenoside Rd ameliorated CCl4-induced ALI in mice, which was related to the reduction of ferroptosis. Simultaneously, the ginsenoside Rd-mediated inhibition of the cGAS/STING pathway contributed to its antiferroptosis effect. In conclusion, our results suggested that ginsenoside Rd inhibited ferroptosis via the cGAS/STING pathway, thereby protecting mice from CCl4-induced ALI. These results suggested ginsenoside Rd may be used as a potential intervention treatment against CCl4-induced ALI.

Ginsenoside Rg3 (Rg3) is an adjuvant antitumor drug, while ginsenoside Re (Re) is an adjuvant antidiabetic drug. Our previous studies demonstrated that Rg3 and Re both have hepatoprotective effects in db/db mice. The present study aimed to observe the renoprotective effects of Rg3 on db/db mice, with Re as the control. The db/db mice were randomly assigned to receive daily oral treatment with Rg3, Re or vehicle for 8 weeks. Body weight and blood glucose were examined weekly. Blood lipids, creatinine, and BUN were examined by biochemical assay. Hematoxylin and eosin and Masson staining were used for pathological examination. The expression of peroxisome proliferator-activated receptor gamma (PPAR gamma) and inflammation and fibrosis biomarkers was examined by immunohistochemical and reverse transcription-quantitative PCR. Although neither had a significant effect on body weight, blood glucose or lipids, Rg3 and Re were both able to decrease the creatinine and blood urea nitrogen levels of db/db mice to levels similar to those of wild type mice and inhibit pathological changes. The expression of PPAR gamma was upregulated and biomarkers of inflammation and fibrosis were downregulated by Rg3 and Re. The results showed that the potential of Rg3 as a preventive treatment of diabetic kidney disease was similar to that of Re.

目的 比较山核桃壳、山沙土、玉米芯及玉米秸秆栽培土壤培育的灵芝超微粉对小鼠免疫功能的影响.方法 清洁级ICR雄性小鼠随机分为对照组,灵芝1号组,灵芝2号组,灵芝3号组及灵芝4号低、高剂量组,每组10只.对照组每日灌胃给予0.5％羧甲基纤维素钠20ml/kg,灵芝1号、灵芝2号、灵芝3号及灵芝4号低、高剂量组分别灌胃给予不同土壤种植的灵芝超微粉0.5、1.0 g/kg,每日1次,连续灌胃30天.计算小鼠胸腺、肝脏和脾脏系数,测定碳粒廓清指数K,吞噬指数α,血清溶血素生成,T淋巴细胞转化功能和NK细胞活性.结果 灵芝1号,灵芝2号,灵芝3号及灵芝4号组均能明显增强小鼠脏器系数,廓清指数和吞噬指数,促进血清溶血素生成和T淋巴细胞增殖,提高NK细胞活性.结论 山核桃壳、山沙土,玉米芯及玉米秸秆土壤培育的灵芝超微粉对小鼠非特异性及特异性免疫功能均具有增强作用,各组间无明显差异.

Context Panax ginseng C. A. Meyer (Araliaceae) is a famous Asian medicine. Ginsenoside Rc is a component isolated from Panax ginseng. Objective This study evaluates the effect of ginsenoside Rc on myocardial ischaemic injury. Materials and methods Male Swiss mice were subcutaneously injected with 50 mg/kg isoproterenol once a day for three days. Ginsenoside Rc (10, 20, or 40 mg/kg) was intragastrically administered 1 h after isoproterenol injection. The mice in the control group were subcutaneously injected with normal saline and intragastrically given 0.5% CMC-Na. CK-MB and troponin T were assayed. Histopathological examination of myocardium was conducted. The expression of Nrf2, GCLC, GCLM and HO-1 in heart tissues was evaluated by Western blot. Results In myocardial ischaemic mice, ginsenoside Rc reduced the levels of CK-MB (197.1 +/- 15.7, 189.9 +/- 19.0, 184.0 +/- 14.4 vs. 221.6 +/- 27.9) and troponin T (10.3 +/- 1.7, 9.5 +/- 1.3, 8.7 +/- 1.7 vs. 13.4 +/- 2.4). Ginsenoside Rc attenuated the necrosis and inflammatory cells infiltration in myocardium. Furthermore, ginsenoside Rc not only decreased the contents of MDA, TNF-alpha but also increased GSH level in the heart tissues. The expression of Nrf2, GCLC, GCLM and HO-1 was significantly increased in the animals treated with ginsenoside Rc. ML385, an Nrf2 inhibitor, blocked partially the ginsenoside Rc-mediated cardioprotective effect. Ginsenoside Rc attenuated myocardial ischaemic injury in mice, which may be, in part, through its antioxidative and anti-inflammatory effects. Conclusions This study indicated that ginsenoside Rc might be a novel candidate for treatment of myocardial ischaemia.

Panax ginseng polysaccharides (GPS) are isolated from Panax ginseng C. A. Meyer, which has many pharmacological activities. However, although the protective effect of GPS on inflammatory bowel disease (IBD) has been characterized, its mechanism has not yet been fully elucidated. In the present study, we clarified it effect on IBD in mice and studied the mechanism of reducing inflammation. IBD model was established in mice by administrating dextran sulfate sodium (DSS) in drinking water for 7 days. Our results showed that GPS treatment significantly relieved disease activity index, colon length shortening and pathological changes in colonic tissue. Furthermore, GPS treatment significantly reduced oxidative stress and inflammatory cytokines in the colonic tissue via inhibiting JAK2/STAT1/NLRP3 inflammasome signalling pathway. In conclusion, these results demonstrated that GPS could attenuate inflammatory response via inhibiting JAK2/STAT1/NLPR3 inflammasome signalling pathway. Hence, GPS may be a potential natural medicine to inhibit JAK2/STAT1/NLRP3 inflammasome signalling pathway and reduce inflammation in IBD.

目的 检测并比较不同栽培土壤条件下种植的灵芝经济性状、三萜及甾醇类成分、多糖类成分以及水分和浸出物含量,探讨山核桃壳、山沙土、玉米芯及玉米秸秆4种栽培土壤对灵芝质量的影响.方法 采用《中国药典》(2020版)方法,对山核桃壳、山沙土、玉米芯及玉米秸秆栽培土壤培育的灵芝中灵芝三萜及甾醇、多糖、水分及浸出物含量进行分析测定.结果 4种栽培土壤所种植的灵芝三萜及甾醇、多糖、水分及浸出物含量均符合药典要求.其中,玉米秸秆土壤栽培的灵芝样本中检测到的灵芝三萜及甾醇、多糖成分比其他三组较高,且具有较高的浸出物含量及较低的含水量.结论 山核桃壳、玉米芯及玉米秸秆土壤均可代替山沙土培育灵芝.

The leaves of Murraya paniculata (L.) Jack were used as spices in China for many years. Flavonoids are the main components of it. However, no study has determined whether the total flavonoids of Murraya paniculata (L.) Jack (TFMP) has preventive effects on diabetic cardiomyopathy (DCM).The present study investigated the effect of TFMP on DCM. STZ was administered along with a high-fat diet to induce diabetes in rats. Parallel experiments were performed using H9c2 cells exposed to high glucose. Diabetic rats showed serious histological changes and increased levels of cardiac function markers. The markers of ROS, inflammation and apoptosis were also increased significantly, but the antioxidant defenses were decreased. Treatment with TFMP alleviated histological alteration in the myocardium. TFMP suppressed oxidative stress, inflammation and apoptosis. Our results demonstrate that the protective of TFMP on DCM is associated with increasing Nrf2 and HO-1 gene expression and inhibiting oxidative stress, inflammation and apoptosis.

20(S)-protopanaxadiol (PPD) is an active natural product which is transformed from protopanaxadiol-type ginsenosides. The present study was conducted to evaluate the effects of PPD on myocardial ischemia/reperfusion (I/R) injury in a rat model. PPD (20mg/kg) or positive-control drug Diltiazem (10mg/kg) was administered daily for 7 days before left anterior descending I/R operation. After 2-hour reperfusion, changes of cardiac morphology, structure, and function were evaluated by HE staining and echocardiography. Myocardial infarct size was assessed using nitroblue tetrazolium staining. The activities of cardiac enzymes in serum were also evaluated. Cardiomyocyte apoptosis was detected using the terminal dUTP nick end labelling (TUNEL) assay. The extent of oxidative stress was evaluated according to the activities of superoxide dismutase (SOD) and glutathione per oxidase (GPx) and the levels of malondialdehyde (MDA). Western blot and immunohistochemistry were used to determine the expression of apoptosis associated proteins, including Bcl-2, Bax, cleaved Caspase-3, cleaved Caspase-9, and cytochrome C. According to the results, PPD reduced I/R‑induced increases in myocardial infarct size and improved cardiac function. Furthermore, PPD decreased cardiomyocyte apoptosis on TUNEL staining, which was verified by increased Bcl-2, and decreased expression of Bax, cytochrome C, cleaved Caspase-9, and cleaved Caspase-3 in I/R rat myocardium. Additionally, PPD reduced MDA levels and increased the anti-oxidative capacity by upregulating the activities of SOD and GPx. Taken together, the results suggest that PPD serves a protective role against oxidative stress and cardiomyocyte apoptosis during myocardial ischemia/reperfusion injury.

Ginsenoside Rc is one of the cardinal bioactive components of Panax ginseng. The present study aimed to investigate whether ginsenoside Rc exerted protective effects against acute cold exposure-induced myocardial injury in rats. Forty rats were randomly assigned into four groups: Control, model, ginsenoside Rc 10 mg/kg, and 20 mg/kg groups. Rats were intragastrically administrated with ginsenoside Rc (10, 20 mg/kg) or vehicle daily for 7 days. On the seventh day, all rats except the control group were exposed to low temperature. Cardiac function, myocardial enzyme activities, hemorheology, and inflammatory response were detected. Histopathological examination and apoptosis of cardiac tissues were performed. The expressions of silent information regulator 1 (SIRT1), B-cell lymphoma (Bcl-2), Bcl-2-associated X (Bax), procaspase-3, and the mRNA (messenger RNA) level of SIRT1 were measured by western blot and real-time quantitative polymerase chain reaction (PCR) analysis. Ginsenoside Rc significantly improved cardiac function, diminished the activities of lactate dehydrogenase (LDH), aspartate aminotransferase, and creatine kinase isoenzyme (CK-MB), and regulated abnormal hemorheology in acute cold-exposed rats (p < 0.05 or p < 0.01). Furthermore, ginsenoside Rc could attenuate myocardial histological changes and structural abnormalities, decrease apoptotic cells and reduce the mRNA levels and activity of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and IL-6 (p < 0.01). In addition, ginsenoside Rc upregulated the expressions of SIRT1, Bcl-2, and procaspase-3 and downregulated that of Bax (p < 0.01). The changes in both the mRNA and protein expression levels of SIRT1 were similar. The results of the current study suggested that ginsenoside Rc could alleviate acute cold exposure-induced myocardial injury in rats by inhibiting cardiomyocyte apoptosis via regulating SIRT1 expression and attenuating the inflammatory responses. PRACTICAL APPLICATION: The current study indicated that ginsenoside Rc could alleviate acute cold exposure-induced myocardial injury in rats. Ginsenoside Rc could be potentially used as a bioactive ingredient in processed functional food products or food supplements to prevent from acute cold exposure-induced myocardial injury.

Context Panax ginseng C.A. Meyer (Araliaceae) has cardioprotective effects. Ginsenosides are responsible for most of the pharmacological activities of ginseng. Objective This study investigates the effect of ginsenoside Rg2 on myocardial fibrosis in myocardial ischaemia rats. Materials and methods Male Wistar rats were divided into control, isoproterenol, ginsenoside Rg2 (5, 20 mg/kg) groups (n = 8). The rats were subcutaneously injected with isoproterenol (5 mg/kg) or normal saline (control group) once daily for 7 days. The animals were intragastrically treated with ginsenoside Rg2 or 0.5% CMC-Na (control and isoproterenol groups) daily for 28 days. At day 28, cardiac function, myocardial fibrosis, and TGF-beta 1/Smad signalling pathway were evaluated. Results Compared with myocardial ischaemic rats, ginsenoside Rg2 at doses of 5, 20 mg/kg abated partially the augment of LVEDP (8.9 +/- 1.3 vs. 7.5 +/- 0.7, 7.2 +/- 1.0 mmHg) and the decreases of the LVSP (96.75 +/- 13.2 vs. 118.3 +/- 19.4, 124.3 +/- 21.3 mmHg), the + dp/dt (2142.8 +/- 309.3 vs. 2598.6 +/- 404.0, 2661.5 +/- 445.2 mmHg/s), and the -dp/dt (1996.3 +/- 306.3 vs. 2476.6 +/- 289.7, 2509.6 +/- 353.1 mmHg/s). Ginsenoside Rg2 (9.2 +/- 0.9%, 8.5 +/- 0.8%) alleviated myocardial fibrosis when compared with the isoproterenol group (10.1 +/- 1.0%), which was accompanied by suppressed TGF-beta 1/Smad signalling in heart tissues. Conclusions Ginsenosides from ginseng possess the property of alleviating myocardial fibrosis, improving cardiac function after myocardial ischaemia. Ginsenosides may be promising agents for improving the outcomes of patients with myocardial ischaemia.

Background: Pseudo-ginsenoside-Rh2 (pseudo-G-Rh2), a novel derivative of ginseno-side Rh2, is reported to exert a pro-apoptotic effect on various malignancies. However, whether this anti-cancer action of pseudo-G-Rh2 involves autophagy remains to be determined and ex-plored. Objective: The objective of this study was to investigate the pseudo-G-Rh2-induced apoptosis and autophagy and the underlying mechanism. Methods: In the present study, the MTT assay was used for evaluating cell viability, and the lactate dehydrogenase (LDH) assay was performed to assess cell toxicity. Autophagy evaluation was per -formed using monodansylcadaverine (MDC) staining and transmission electron microscopy (TEM). The levels of autophagy-associated and apoptosis-associated proteins were determined us -ing Western blotting. The Annexin V-FITC/propidium iodide (PI) assay was used to assess apopto-sis. Results: The Annexin V-FITC/PI assay revealed that the percentage of apoptotic cells in HepG2 cells at concentrations 0, 20, 40, and 60 mu M was 3.75%+/- 1.37%, 5.70%+/- 1.04%, 12.30%+/- 2.10%, and 34.26%+/- 4.73%, respectively. Pseudo-G-Rh2 was observed to significantly increase the expres-sions of BAX, cleaved-caspase-3, and cleaved-caspase-9, while it decreased the Bcl-2 expression. MDC and TEM analysis revealed that pseudo-G-Rh2 at concentrations 20, 40, and 60 mu M signifi-cantly facilitated the accumulation of autophagosomes and autolysosomes within the HepG2 cells. Moreover, pseudo-G-Rh2 significantly increased the expressions of LC3 II/LC3 I and Beclin-1 and decreased the expression of p62. The Annexin V-FITC/PI assay also revealed that in comparison to the pseudo-G-Rh2 group, the concurrent treatment with pseudo-G-Rh2 and an autophagy inhibitor (CQ or 3-MA) significantly induced distinct apoptosis. In addition, pseudo-G-Rh2 activated AMPK and inhibited the PI3K/Akt/mTOR pathway in a concentration-dependent manner. Pseu-do-G-Rh2 is similar to the current patents, which enhanced its anti-cancer activity by combining with autophagy inhibitors. Conclusion: Pseudo-G-Rh2 could induce protective autophagy in HepG2 cells, at least in part, via AMPK and the PI3K/Akt/mTOR pathway.

目的 研究20(S)-原人参二醇(20(S)-PPD)对人结直肠癌SW620细胞迁移和侵袭的影响.方法 20(S)-PPD处理SW620细胞24h,MTT检测20(S)-PPD对SW620细胞增殖的抑制情况,Transwell小室检测细胞迁移和侵袭能力.结果 20(S)-PPD在>40μM剂量时明显杀伤SW620细胞(P<0.05),但20(S)-PPD在10、20、25及30μM剂量时对SW620细胞无显著细胞杀伤作用;20(S)-PPD(10、20及30μM)可明显抑制SW620细胞迁移和侵袭的能力(P<0.05);20(S)-PPD可提高E-cadherin蛋白表达,降低Vimentin蛋百表达.结论 20(S)-PPD在低剂量时可以抑制人结直肠癌SW620细胞的侵袭能力.