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Fitoterapia Jul 2024Notoginseng leaf triterpenes (PNGL), derived from the dried stems and leaves of P. notoginseng, is a phytoestrogen that exerts many neuroprotective effects in vivo and...
Notoginseng leaf triterpenes (PNGL), derived from the dried stems and leaves of P. notoginseng, is a phytoestrogen that exerts many neuroprotective effects in vivo and in vitro of ischemic stroke. However, its impact on neurological restoration specifically in relation to angiogenesis following ischemic stroke remains unexplored. The aim of this study was to assess the effects of PNGL on angiogenesis subsequent to ischemic stroke. Male Sprague-Dawley rats were utilized in this study and were subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). Post-ischemia, PNGL were administered through intraperitoneal (i.p.) injection. The high-performance liquid chromatography (HPLC) fingerprinting, triphenyltetrazolium chloride (TTC) staining, immunofluorescent staining, network pharmacology and western blot analyses were assessed to determine the therapeutical effect and molecular mechanisms of PNGL on cerebral ischemia/reperfusion injury. Our findings demonstrate that PNGL effectively reduced infarct volume, enhanced cerebral blood flow, and induced angiogenesis in rats subjected to MCAO/R. Notably, PNGL also facilitated neuronal proliferation and migration in HUMECs in vitro. The proangiogenic effects of PNGL were found to be linked to the activation of the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis, as well as the activation of neurological function. Our study provides evidence that PNGL hold promise as an active ingredient of inducing proangiogenic effects, potentially through the activation of the Nrf2 pathway and the AMPK/SIRT1-mediated PGC-1/ERα axis. These findings contribute to the understanding of novel mechanisms involved in the restoration of neurological function following PNGL treatment for ischemic stroke.
Topics: Animals; Rats, Sprague-Dawley; Male; NF-E2-Related Factor 2; Rats; Sirtuin 1; Ischemic Stroke; Triterpenes; Panax notoginseng; Plant Leaves; Humans; Neuroprotective Agents; AMP-Activated Protein Kinases; Signal Transduction; Infarction, Middle Cerebral Artery; Neovascularization, Physiologic; China; Reperfusion Injury; Angiogenesis Inducing Agents; Angiogenesis
PubMed: 38823597
DOI: 10.1016/j.fitote.2024.106045 -
Phytomedicine : International Journal... Jul 2024Aberrant activation of autophagy in triple-negative breast cancer (TNBC) has led researchers to investigate potential therapeutic strategies targeting this process. The...
BACKGROUND
Aberrant activation of autophagy in triple-negative breast cancer (TNBC) has led researchers to investigate potential therapeutic strategies targeting this process. The regulation of autophagy is significantly influenced by METTL3. Our previous research has shown that the Panax ginseng-derived compound, 20(R)-panaxatriol (PT), has potential as an anti-tumor agent. However, it remains unclear whether PT can modulate autophagy through METTL3 to exert its anti-tumor effects.
OBJECTIVE
Our objective is to investigate whether PT can regulate autophagy in TNBC cells and elucidate the molecular mechanisms.
STUDY DESIGN
For in vitro experiments, we employed SUM-159-PT and MDA-MB-231 cells. While in vivo experiments involved BALB/c nude mice and NOD/SCID mice.
METHODS
In vitro, TNBC cells were treated with PT, and cell lines with varying expression levels of METTL3 were established. We assessed the impact on tumor cell activity and autophagy by analyzing autophagic flux, Western Blot (WB), and methylation levels. In vivo, subcutaneous transplantation models were established in BALB/c nude and NOD/SCID mice to observe the effect of PT on TNBC growth. HE staining and immunofluorescence were employed to analyze histopathological changes in tumor tissues. MeRIP-seq and dual-luciferase reporter gene assays were used to identify key downstream targets. Additionally, the silencing of STIP1 Homology And U-Box Containing Protein 1 (STUB1) explored PT's effects. The mechanism of PT's action on STUB1 via METTL3 was elucidated through mRNA stability assays, mRNA alternative splicing analysis, and nuclear-cytoplasmic mRNA separation.
RESULTS
In both in vivo and in vitro experiments, it was discovered that PT significantly upregulates the expression of METTL3, leading to autophagy inhibition and therapeutic effects in TNBC. Simultaneously, through MeRIP-seq analysis and dual-luciferase reporter gene assays, we have demonstrated that PT modulates STUB1 via METTL3, influencing autophagy in TNBC cells. Furthermore, intriguingly, PT extends the half-life of STUB1 mRNA by enhancing its methylation modification, thereby enhancing its stability.
CONCLUSION
In summary, our research reveals that PT increases STUB1 mA modification through a METTL3-mediated mechanism in TNBC cells, inhibiting autophagy and further accentuating its anti-tumor properties. Our study provides novel mechanistic insights into TNBC pathogenesis and potential drug targets for TNBC.
Topics: Animals; Triple Negative Breast Neoplasms; Humans; Autophagy; Female; Mice, Inbred BALB C; Cell Line, Tumor; Methyltransferases; Mice, Nude; Ubiquitin-Protein Ligases; Mice, SCID; Mice, Inbred NOD; Mice; Antineoplastic Agents, Phytogenic; Xenograft Model Antitumor Assays; Panax; Adenosine
PubMed: 38823344
DOI: 10.1016/j.phymed.2024.155537 -
Phytomedicine : International Journal... Jul 2024Oxidative stress is the main cause of many diseases, but because of its complex pathogenic factors, there is no clear method for treating it. Ginseng total saponin (GTS)...
BACKGROUND
Oxidative stress is the main cause of many diseases, but because of its complex pathogenic factors, there is no clear method for treating it. Ginseng total saponin (GTS) an important active ingredients in Panax ginseng C.A. Mey (PG) and has potential therapeutic ability for oxidative stress due to various causes. However, the molecular mechanism of GTS in the treating oxidative stress damage in red blood cells (RBCs) is still unclear.
PURPOSE
This study aimed to examine the protective effect of GTS on RBCs under oxidative stress damage and to determine its potential mechanism.
METHODS
The oxidative stress models of rat RBCs induced by hydrogen peroxide (HO) and exhaustive swimming in vivo and in vitro was used. We determined the cell morphology, oxygen carrying capacity, apoptosis, antioxidant capacity, and energy metabolism of RBCs. The effect of tyrosine phosphorylation (pTyr) of Band 3 protein on RBCs glycolysis was also examined.
RESULTS
GTS reduced the hemolysis of RBCs induced by HO at the lowest concentration. Moreover, GTS effectively improved the morphology, enhanced the oxygen carrying capacity, and increased antioxidant enzyme activity, adenosine triphosphate (ATP) levels, and adenosine triphosphatase (ATPase) activity in RBCs. GTS also promoted the expression of membrane proteins in RBCs, inhibited pTyr of Band 3 protein, and further improved glycolysis, restoring the morphological structure and physiological function of RBCs.
CONCLUSIONS
This study shows, that GTS can protect RBCs from oxidative stress damage by improving RBCs morphology and physiological function. Changes in pTyr expression and its related pTyr regulatory enzymes before and after GTS treatment suggest that Band 3 protein is the main target of GTS in the treating endogenous and exogenous oxidative stress. Moreover, GTS can enhance the glycolytic ability of RBCs by inhibiting pTyr of Band 3 protein, thereby restoring the function of RBCs.
Topics: Oxidative Stress; Panax; Erythrocytes; Saponins; Animals; Glycolysis; Hydrogen Peroxide; Tyrosine; Rats, Sprague-Dawley; Male; Phosphorylation; Rats; Hemolysis; Antioxidants; Anion Exchange Protein 1, Erythrocyte; Apoptosis
PubMed: 38823342
DOI: 10.1016/j.phymed.2024.155785 -
IUBMB Life Jun 2024Ginsenosides are the primary component discernible from ginseng, including Rb1, Rb2, Rd, Rg1, Rg2, and compound K, and so forth. They have been shown to have multiple... (Review)
Review
Ginsenosides are the primary component discernible from ginseng, including Rb1, Rb2, Rd, Rg1, Rg2, and compound K, and so forth. They have been shown to have multiple pharmacological activities. In recent years, more and more studies have been devoted to the neuroprotection of various ginsenosides against neurological diseases and their potential mechanisms. This paper comprehensively summarizes and reviews the neuroprotective effects of various ginsenosides on neurological diseases, especially acute and chronic neurodegenerative diseases, and their mechanisms, as well as their potential therapeutic applications to promote neuroprotection in disease prevention, treatment, and prognosis. Briefly, ginsenosides exert effective neuroprotective effects on neurological conditions, including stroke, Alzheimer's disease, Parkinson's disease, and brain/spinal cord injuries through a variety of molecular mechanisms, including anti-inflammatory, antioxidant, and anti-apoptotic. Among them, some signaling pathways play important roles in related processes, such as PI3K/Akt, TLR4/NF-κB, ROS/TXNIP/NLRP3, HO-1/Nrf2, Wnt/β-catenin, and Ca pathway. In conclusion, the present study reviews the research progress on the neuroprotective effects of ginsenosides in the last decade, with the aim of furnishing essential theoretical underpinning and effective references for further research and exploration of the multiple medicinal values of Chinese herbal medicines and their small molecule compounds, including ginseng and panax ginseng. Because there is less evidence in the existing clinical studies, future research should be focused on clinical trials in order to truly reflect the clinical value of various ginsenosides for the benefit of patients.
PubMed: 38822647
DOI: 10.1002/iub.2862 -
Chemistry & Biodiversity May 2024. The escalating prevalence of male infertility in the contemporary era across the globe can be largely attributed to environmental pollution, which is the common...
. The escalating prevalence of male infertility in the contemporary era across the globe can be largely attributed to environmental pollution, which is the common etiological factor due to the ubiquitous presence of the environmental contaminants. Bisphenol A is recognized as an endocrine-disrupting chemical that has adverse effects on both male and female reproductive systems. On the other hand, numerous studies have demonstrated that Panax ginseng possessed the potential to improve male infertility parameters; promote spermatogenesis, recover the quality and motility of sperm and enhance testicular functions as it acted as a natural androgen supplement. The objective of this review is to offer a summary of the findings obtained from the current research data on the insult of bisphenol A (BPA) on male infertility and its supposed mode of action, as well as shed light on the potent ameliorative role of Panax ginseng extract, with a special focus on the mechanism behind its action. This review delivers a clear understanding of BPA mechanism of action on male infertility and the presumed risks deriving from its exposure. Also, this review provides evidence for the functional role of Panax ginseng extract in restoring male fertility.
PubMed: 38818674
DOI: 10.1002/cbdv.202400480 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... Apr 2024This study observed the effects of Notoginseng Radix et Rhizoma on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin complex...
[Mechanism of Notoginseng Radix et Rhizoma in regulating PI3K/Akt/mTORC1-mitochondrial energy metabolism to treat chronic renal failure in rats with blood stasis syndrome].
This study observed the effects of Notoginseng Radix et Rhizoma on the phosphatidylinositol 3-kinase(PI3K)/protein kinase B(Akt)/mammalian target of rapamycin complex 1(mTORC1) signaling pathway and mitochondrial energy metabolism in the rat model of adriamycin-induced renal fibrosis with blood stasis syndrome to explore the mechanism of Notoginseng Radix et Rhizoma in protecting the kidney. Thirty male rats with adriamycin-induced renal fibrosis were randomized into model, low-, medium-, and high-dose Notoginseng Radix et Rhizoma, and positive control groups(n=6). Six clean SD male rats were selected into the normal group. The normal group and model group were administrated with normal saline, and other groups with corresponding drugs. After 8 weeks of treatment, the renal function, renal pathology, adenosine triphosphate(ATP) levels, Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities, and the protein levels of ATP5B, mTORC1, 70 kDa ribosomal protein S6 kinase(P70S6K), P85, Akt, p-Akt, and SH2-containing inositol phosphatase(SHIP2) in the renal tissue were determined. Compared with the normal group, the model group showed elevated levels of blood urea nitrogen(BUN) and serum creatinine(SCr)(P<0.01). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control lowered the levels of BUN and SCr, which were significant in the medium-and high-dose Noto-ginseng Radix et Rhizoma groups and the positive control group(P<0.05). Compared with the model group, Notoginseng Radix et Rhizoma and the positive control alleviated the pathological changes in the renal tissue, such as vacuolar and fibroid changes, glomerulus atrophy, cystic expansion of renal tubules, and massive infiltration of inflammatory cells. Compared with the normal group, the model group showed decreased mitochondrial ATP content and Na~+-K~+-ATPase and Ca~(2+)-Mg~(2+)-ATPase activities in the renal tissue(P<0.05), and medium-and high-dose Notoginseng Radix et Rhizoma and positive control mitigated such decreases(P<0.05). Compared with the model group, medium-and high-dose Notoginseng Radix et Rhizoma and the positive control up-regulated the protein levels of ATP5B and SHIP2 and down-regulated the protein levels of mTORC1, P70S6K, P85, Akt, and p-Akt(P<0.05 or P<0.01 or P<0.001). Notoginseng Radix et Rhizoma may exert an anti-fibrosis effect by inhibiting the activation of the PI3K/Akt/mTORC1 pathway to restore mitochondrial energy metabolism, thus protecting the kidney.
Topics: Animals; Male; Rats; Proto-Oncogene Proteins c-akt; Rats, Sprague-Dawley; Mechanistic Target of Rapamycin Complex 1; Panax notoginseng; Mitochondria; Energy Metabolism; Drugs, Chinese Herbal; Phosphatidylinositol 3-Kinases; Rhizome; Humans; Signal Transduction; Kidney; Renal Insufficiency
PubMed: 38812201
DOI: 10.19540/j.cnki.cjcmm.20231009.403 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... Apr 2024Panax ginseng, known as the "king of herbs", is a highly valued medicinal plant, and its medicinal parts include roots, stems, leaves, flowers, and fruits,... (Review)
Review
Panax ginseng, known as the "king of herbs", is a highly valued medicinal plant, and its medicinal parts include roots, stems, leaves, flowers, and fruits, among which the roots are the most commonly used. The main active components of this medicinal plant include triterpenoid saponins, polysaccharides, peptides, and volatile oils. The chemical components and active metabolites endow this herb with a variety of pharmacological effects, and thus this herb is used to treat various diseases and play healthcare roles. Currently, a wide range of preparations of P. ginseng have been officially registered and marketed, including tablets, oral liquids, and injections, which demonstrate good clinical efficacy in regulating immunity, adjuvant treatment of tumors, alleviating fatigue, delaying the aging process, improving glucose and lipid metabolism, treating cardiovascular diseases, and relieving inflammation and pain. The production process and quality standards of these drugs are of great significance to ensure their efficacy. According to the theory that Ginseng Radix et Rhizoma can greatly replenish original Qi, tonify the spleen and lung, promote fluid production to quench thirst, tranquilize mind and enrich the intelligence, this paper systematically summarized the clinical application progress of P. ginseng and rela-ted preparations on the market and prospected the further development of preparations from P. ginseng, providing a reference for further exploring the medicinal value and healthcare function of this herb. The above contents, as an important basis for the in-depth development of P. ginseng and related drugs, increase the possibilities for the application of P. ginseng.
Topics: Panax; Humans; Drugs, Chinese Herbal; Animals
PubMed: 38812184
DOI: 10.19540/j.cnki.cjcmm.20231124.301 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... May 2024Panax ginseng is reputed to be capable of replenishing healthy Qi and bolstering physical strength, and P. notoginseng can resolve blood stasis and alleviate pain. P....
Panax ginseng is reputed to be capable of replenishing healthy Qi and bolstering physical strength, and P. notoginseng can resolve blood stasis and alleviate pain. P. ginseng and P. notoginseng are frequently employed to treat ischemic heart diseases caused by blockages in the heart vessels. Mitochondrial dysfunction often coexists with abnormal mitochondrial morphology, and mitochondrial plasticity and dynamics play key roles in cardiovascular diseases. In this study, primary neonatal rat cardiomyocytes were exposed to 4 hours of hypoxia(H) followed by 2 hours of reoxygenation(R). MitoTracker Deep Red and Hoechst 33342 were used to label mitochondria and nuclei, respectively. Fluorescence images were then acquired using ImageXpress Micro Confocal. Automated image processing and parameter extraction/calculation were carried out using ImagePro Plus. Subsequently, representative parameters were selected as indicators to assess alterations in mitochondrial morphology and function. The active compounds of P. ginseng and P. notoginseng were screened out and identified based on the UPLC-Triple-TOF-MS results and mitochondrial morphometric parameters. The findings demonstrated that RS-2, RS-4, SQ-1, and SQ-4 significantly increased the values of three key morphometric parameters, including mitochondrial length, branching, and area, which might contribute to rescuing morphological features of myocardial cells damaged by H/R injury. Among the active components of the two medicinal herbs, 20(R)-ginsenoside Rg_3, ginsenoside Re, and gypenoside ⅩⅦ exhibited the strongest protective effects on mitochondria in cardiomyocytes. Specifically, 20(R)-ginsenoside Rg_3 might upregulate expression of optic atrophy 1(OPA1) and mitofusin 2(MFN2), and ginsenoside Re and gypenoside ⅩⅦ might selectively upregulate OPA1 expression. Collectively, they promoted mitochondrial membrane fusion and mitigated mitochondrial damage, thereby exerting protective effects on cardiomyocytes. This study provides experimental support for the discovery of novel therapeutic agents for myocardial ischemia-reperfusion injury from P. ginseng and P. notoginseng and offers a novel approach for large-scale screening of bioactive compounds with cardioprotective effects from traditional Chinese medicines.
Topics: Animals; Rats; Panax; Panax notoginseng; Drugs, Chinese Herbal; Myocytes, Cardiac; Rats, Sprague-Dawley; Cardiotonic Agents; Chromatography, High Pressure Liquid; Mitochondria; Mass Spectrometry
PubMed: 38812177
DOI: 10.19540/j.cnki.cjcmm.20231221.701 -
Zhongguo Zhong Yao Za Zhi = Zhongguo... May 2024This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were...
This study investigated the effects and mechanisms of total saponins of Panax japonicus(TSPJ) against liver injury induced by acetaminophen(APAP). Male Kunming mice were randomly divided into a blank control group, TSPJ group(200 mg·kg~(-1), ig), model group, APAP+ TSPJ low-dose group(50 mg·kg~(-1), ig), APAP+ TSPJ medium-dose group(100 mg·kg~(-1), ig), APAP+ TSPJ high-dose group(200 mg·kg~(-1), ig), and APAP+ N-acetyl-L-cysteine group(200 mg·kg~(-1), ip). The administration group received the corresponding medications via ig or ip once a day for 14 consecutive days. After the last administration for one hour, except for the blank control group and TSPJ group, all groups of mice were given 500 mg·kg~(-1) APAP by gavage. After 24 hours, mouse serum and liver tissue were collected for serum alanine aminotransferase(ALT), aspartate aminotransferase(AST), reactive oxygen species(ROS), tumor necrosis factor alpha(TNF-α), interleukin-1 beta(IL-1β), cyclooxygenase-2(COX-2), IL-6, IL-4, IL-10, as well as lactate dehydrogenase(LDH), glutathione(GSH), superoxide dismutase(SOD), catalase(CAT), total antioxidant capacity(T-AOC), malondialdehyde(MDA), and myeloperoxidase(MPO) liver tissue. Hematoxylin-eosin staining was used to observe the morphological changes of liver tissue. The mRNA expression levels of lymphocyte antigen 6G(Ly6G), galectin 3(Mac-2), TNF-α, IL-1β, COX-2, IL-6, IL-4, and IL-10 in liver tissue were determined by quantitative real-time polymerase chain reaction(PCR). Western blot was utilized to detect the protein expression levels of Ly6G, Mac-2, extracellular regulated protein kinases(ERK), phosphorylated extracellular regulated protein kinases(p-ERK), COX-2, inhibitor of nuclear factor κB protein α(IκBα), phosphorylated inhibitor of nuclear factor κB protein α(p-IκBα), and nuclear factor-κB subunit p65(NF-κB p65) in cytosol and nucleus in liver tissue. The results manifested that TSPJ dramatically reduced liver coefficient, serum ALT, AST, ROS, TNF-α, IL-1β, IL-6, and COX-2 levels, LDH, MPO, and MDA contents in liver tissue, and mRNA expressions of TNF-α, IL-1β, and IL-6 in APAP-induced liver injury mice. It prominently elevated serum IL-4 and IL-10 levels, GSH, CAT, SOD, and T-AOC contents, and mRNA expressions of IL-4 and IL-10 in liver tissue, improved the degree of liver pathological damage, and suppressed neutrophil infiltration and macrophage recruitment in liver tissue. In addition, TSPJ lessened the mRNA and protein expressions of neutrophil marker Ly6G, macrophage marker Mac-2, and COX-2 in liver tissue, protein expressions of p-ERK, p-IκBα, and NF-κB p65 in nuclear, and p-ERK/ERK and p-IκBα/p-IκBα ratios and hoisted protein expression of NF-κB p65 in cytosol. These results suggest that TSPJ has a significant protective effect on APAP-induced liver injury in mice, and it can alleviate APAP-induced oxidative damage and inflammatory response. Its mechanism may be related to suppressing ERK/NF-κB/COX-2 signaling pathway activation, thus inhibiting inflammatory cell infiltration, cytokine production, and liver cell damage.
Topics: Animals; Acetaminophen; Mice; Panax; Male; Saponins; NF-kappa B; Chemical and Drug Induced Liver Injury; Cyclooxygenase 2; Liver; Signal Transduction; Humans; Drugs, Chinese Herbal
PubMed: 38812159
DOI: 10.19540/j.cnki.cjcmm.20240205.702 -
PloS One 2024In this study, we aimed to investigate the protective effects of Panax notoginseng and leech (PL) on renal fibrosis and explore the mechanisms underlying their actions....
In this study, we aimed to investigate the protective effects of Panax notoginseng and leech (PL) on renal fibrosis and explore the mechanisms underlying their actions. For this study, we created an adenine-induced renal fibrosis model in SD rats to investigate the protective effect of PL on renal fibrosis and explore its underlying mechanism. Initially, we assessed the renal function in RF rats and found that Scr, BUN, and urine protein content decreased after PL treatment, indicating the protective effect of PL on renal function. Histological analysis using HE and Masson staining revealed that PL reduced inflammatory cell infiltration and decreased collagen fiber deposition in renal tissue. Subsequently, we analyzed the levels of α-SMA, Col-IV, and FN, which are the main components of the extracellular matrix (ECM), using IHC, RT-qPCR, and WB. The results demonstrated that PL was effective in reducing the accumulation of ECM, with PL1-2 showing the highest effectiveness. To further understand the underlying mechanisms, we conducted UPLC-MS/MS analysis on the incoming components of the PL1-2 group. The results revealed several associations between the differential components and antioxidant and mitochondrial functions. This was further confirmed by enzyme-linked immunosorbent assay and biochemical indexes, which showed that PL1-2 ameliorated oxidative stress by reducing ROS and MDA production and increasing GSH and SOD levels. Additionally, transmission electron microscopy results indicated that PL1-2 promoted partial recovery of mitochondrial morphology and cristae. Finally, using RT-qPCR and WB, an increase in the expression of mitochondrial fusion proteins Mfn1, Mfn2, and Opa1 after PL1-2 treatment was observed, coupled with a decline in the expression and phosphorylation of mitochondrial cleavage proteins Fis and Drp1. These findings collectively demonstrate that PL1-2 ameliorates renal fibrosis by reducing oxidative stress and restoring mitochondrial balance.
Topics: Animals; Panax notoginseng; Fibrosis; Mitochondria; Rats; Rats, Sprague-Dawley; Leeches; Male; Kidney; Kidney Diseases; Oxidative Stress; Disease Models, Animal; Extracellular Matrix; Mitochondrial Dynamics
PubMed: 38809875
DOI: 10.1371/journal.pone.0303906