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Extracellular matrix mRNA and protein expression. (A) mRNA level of ECM genes in RG3-treated cell on UV irradiation. (B) Protein level of ECM in RG3-treated cell on UV irradiation. (C) Collagen, elastin, MMP-3, and GAPDH in the immunoprecipitation were quantified by Western blot analyses, as described in the Materials and methods section. Bar heights are means AE SD of three independent experiments. Significant difference from negative control (Non-UV irradiated): *, p < 0.05 and **, p < 0.01. Significant difference from positive control (UV irradiated): #, p < 0.05 and ##, p < 0.01. COL1A1, alpha-1 type I collagen; ECM, extracellular matrix; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; MMP, matrix metalloproteinase; SD, standard deviation; UV, ultraviolet.

Extracellular matrix mRNA and protein expression. (A) mRNA level of ECM genes in RG3-treated cell on UV irradiation. (B) Protein level of ECM in RG3-treated cell on UV irradiation. (C) Collagen, elastin, MMP-3, and GAPDH in the immunoprecipitation were quantified by Western blot analyses, as described in the Materials and methods section. Bar heights are means AE SD of three independent experiments. Significant difference from negative control (Non-UV irradiated): *, p < 0.05 and **, p < 0.01. Significant difference from positive control (UV irradiated): #, p < 0.05 and ##, p < 0.01. COL1A1, alpha-1 type I collagen; ECM, extracellular matrix; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; MMP, matrix metalloproteinase; SD, standard deviation; UV, ultraviolet.

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Background: The efficacy of ginseng, the representative product of Korea, and its chemical effects have been well investigated. The ginsenoside RG3 has been reported to exhibit apoptotic, anticancer, and antidepressant-like effects. Methods: In this report, the putative effect of RG3 on several cellular function including cell survival, differen...

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... evaluated the mRNA levels of ECM proteins in RG3-treated cells after UV irradiation. Our data showed that the mRNA levels of collagen, elastin, and COL1A1 were increased in a dosedependent manner, whereas that of MMP-2 was not (Fig. 3A). Protein extracts of untreated or RG3-treated cells after UV irradiation were analyzed by Western blotting. After UV exposure, the basal expression level of collagen and elastin was decreased dramatically, but RG3-treated cells showed increased collagen and elastin levels compared with untreated controls. The protein content of MMP-3 ...
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... and elastin was decreased dramatically, but RG3-treated cells showed increased collagen and elastin levels compared with untreated controls. The protein content of MMP-3 was increased compared to that of the normal state during UV irradiation, but the expression of MMP-3 decreased in proportion to the concentration of RG3 after UV irradiation (Figs. 3B, ...
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... generation and increase in cell growth, survival, and proliferation and signaling pathways, including ERK-and AKT/PKB-dependent pathways. Treatment of UV-exposed NHFB cells with RG3 extract also resulted in increased levels of ECM proteins such as collagen and elastin but decreased the function of inhibitory collagenases, such as MMP-2 and MMP-3 (Fig. ...
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... evaluated the mRNA levels of ECM proteins in RG3-treated cells after UV irradiation. Our data showed that the mRNA levels of collagen, elastin, and COL1A1 were increased in a dose- dependent manner, whereas that of MMP-2 was not (Fig. 3A). Protein extracts of untreated or RG3-treated cells after UV irradia- tion were analyzed by Western blotting. After UV exposure, the basal expression level of collagen and elastin was decreased dramatically, but RG3-treated cells showed increased collagen and elastin levels compared with untreated controls. The protein con- tent of ...
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... and elastin was decreased dramatically, but RG3-treated cells showed increased collagen and elastin levels compared with untreated controls. The protein con- tent of MMP-3 was increased compared to that of the normal state during UV irradiation, but the expression of MMP-3 decreased in proportion to the concentration of RG3 after UV irradiation (Figs. 3B, ...
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... generation and increase in cell growth, survival, and proliferation and signaling pathways, including ERK-and AKT/PKB-dependent pathways. Treatment of UV-exposed NHFB cells with RG3 extract also resulted in increased levels of ECM proteins such as collagen and elastin but decreased the function of inhibitory collagenases, such as MMP-2 and MMP-3 (Fig. ...

Citations

... Gastrodin is a glucoside extracted from the rhizome of Gastrodia elata Blume [146]. It was found that gastrodin could inhibit the formation of and scavenge oxygen radicals as well as inhibiting LPO in the myocardium during the decompensated stage of heart failure [147,148]. Further, gastrodin was found to inhibit oxidative stress by activating ERK1/2 signaling and reducing GSK-3β overexpression [149]. ...
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The prevalence of cardiovascular diseases (CVDs) is constantly rising, making them a major health burden. In terms of global mortality and morbidity, they are still at the top. An alternate method of treating many illnesses, including CVDs, is the use of medicinal herbs. There is a current, unprecedented push to include herbal remedies into contemporary healthcare systems. The widespread conviction in their safety and the fact that they offer more effective treatment at a lower cost than conventional modern medicines are two of the main factors propelling this movement. However, there has not been enough testing of the purported safety of herbal remedies. As a result, people need to know that medical herbs can be toxic, have possibly fatal side effects, and can interact negatively with other drugs. Experimental evidence suggests that medicinal herbs may be useful in the treatment of cardiovascular diseases (CVDs) due to their ability to inhibit multiple risk factors for these conditions. So, in order to successfully use herbs in CVD therapy, there have been numerous initiatives to transition medicinal herb research from the lab to the clinic. Presented below are cardiovascular diseases (CVDs) and the variables that put people at risk for developing them. Next, we provide a synopsis of herbal medicine's role in the treatment of disease, with a focus on cardiovascular diseases. In addition, information is compiled and examined about the ethnopharmacological therapeutic possibilities and medicinal qualities against cardiovascular diseases of four commonly used plants: ginseng, gingko biloba, ganoderma lucidum, and gymnostemma pentaphyllum. The use of these four plants in the treatment of cardiovascular diseases (CVDs) including myocardial infarction, hypertension, peripheral vascular disorders, coronary heart disease, cardiomyopathies, and dyslipidemias has been well examined. We are also making an effort to describe the current in vitro and in vivo investigations that have attempted to examine the cellular and molecular underpinnings of the four plants' cardio-protective effects. Lastly, we highlighted the effectiveness, safety, and toxicity of these four medicinal herbs by reviewing and reporting the results of current clinical trials. GRAPHICAL ABSTRACT 84 This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)
... The research found a remarkable drop in central and peripheral arterial blood pressure in healthy people after ingesting Rg3 isolated from red ginseng, suggesting that ginsenosides have a preventive effect against cardiovascular disease [87]. Ginsenoside Rg3 restored the morphology and function of normal human dermal fibroblasts under UV irradiation and promoted protein expression related to antioxidant activity and cell proliferation [88]. ...
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Immune disorders have become one of the public health problems and imposes a serious economic and social burden worldwide. Ginsenosides, the main active constituents of ginseng, are regarded as a novel supplementary strategy for preventing and improving immune disorders and related diseases. This review summarized the recent research progress of ginsenosides in immunomodulation and proposed future directions to promote the development and application of ginsenosides. After critically reviewing the immunomodulatory potential of ginsenosides both in vitro and in vivo and even in clinical data of humans, we provided a perspective that ginsenosides regulated the immune system through activation of immune cells, cytokines, and signaling pathways such as MAPK, PI3K/Akt, STAT, and AMPK, as well as positively affected immune organs, gut flora structure, and systemic inflammatory responses. However, the evidence for the safety and efficacy of ginsenosides is insufficient, and the immune pathways of ginsenosides remain incompletely characterized. We believe that this review will provide a valuable reference for further research on ginsenosides as dietary supplements with immunomodulatory effects.
... RG effectiveness has long been researched using various ways, and studies represent that RG protects the human body [53]. However, studies on the active ingredients of non-saponinoriented RGE have been very limited. ...
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Background: Korean Red Ginseng is a major source of bioactive substances such as ginsenosides. Efficacy of red ginseng extract (RGE), which contains not only saponins but also various non-saponins, has long been studied. In the water-soluble component-rich fraction of RGE (WS), a byproduct generated in the process of extracting saponins from the RGE, we identified previously unidentified molecules and confirmed their efficacy. Methods: The RGE was prepared and used to produce WS, whose components were isolated sequentially according to their water affinity. The new compounds from WS were fractionized and structurally analyzed using nuclear magnetic resonance spectroscopy. Physiological applicability was evaluated by verifying the antioxidant and anti-inflammatory efficacies of these compounds in vitro. Results: High-performance liquid chromatography confirmed that the obtained WS comprised 11 phenolic acid and flavonoid substances. Among four major compounds from fractions 1-4 (F1-4) of WS, two compounds from F3 and F4 were newly identified in red ginseng. The analysis results show that these compound molecules are member of the maltol-structure-based glucopyranose series, and F1 and F4 are particularly effective for decreasing oxidative stress levels and inhibiting nitric oxide secretion, interleukin (IL)-1β and IL-6, and tumor necrosis factor-α. Conclusion: Our findings suggest that a few newly identified maltol derivatives, such as red ginseng-derived non-saponin in the WS, exhibit antioxidant and anti-inflammatory effects, making them viable candidates for application to pharmaceutical, cosmetic, and functional food materials.
... Therefore, Rg3 was selected to be used in our study. Ginsenoside Rg3 (Rg3), a rare saponin in ginseng, was reported to have pharmacological effects, such as antiinflammatory, antioxidant, anticancer 10 , antiulcer 11 , neuroprotective 12 , anti-fatigue 13 , anti-aging activities 14 and adjuvant therapy of rheumatoid arthritis 15 . Recently, there have also been some research reports on the role of Rg3 in the effect of allergic lower airway diseases. ...
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Increasing studies have demonstrated that ginsenoside Rg3 (Rg3) plays an important role in the prevention and treatment of various diseases, including allergic lower airway inflammation such as asthma. To investigate the role of Rg3 in allergic upper airway disease, the effect and therapeutic mechanism of Rg3 in allergic rhinitis (AR) were studied. Ovalbumin-induced AR model mice were intragastrically administered with Rg3. Nasal symptoms, levels of IgE, IL-4, IL-5, IL-13, SOD and MDA in serum, and histopathological analysis of nasal mucosa were used to evaluate the effect of Rg3 on ameliorating AR in mice. Moreover, nasal mucosa samples from the normal control group, AR model group and high dosage of Rg3 were collected to perform omics analysis. The differentially expressed genes and significantly changed metabolites were screened based on transcriptomics and metabolomics analyses, respectively. Integrative analysis was further performed to confirm the hub genes, metabolites and pathways. After Rg3 intervention, the nasal symptoms and inflammatory infiltration were effectively improved, the levels of IgE, IL-4, IL-5, IL-13 and MDA were significantly reduced, and the level of SOD was obviously increased. The results of the qRT-PCR assay complemented the transcriptomic findings. Integrated analysis showed that Rg3 played an anti-AR role mainly by regulating the interaction network, which was constructed by 12 genes, 8 metabolites and 4 pathways. Our findings suggested that Rg3 had a therapeutic effect on ovalbumin-induced AR in mice by inhibiting inflammation development and reducing oxidative stress. The present study could provide a potential natural agent for the treatment of AR.
... Ginsenoside Rg3, one of the main components of steamed Korean ginseng (Panax ginseng Meyer), has been widely considered as a representative bioactive component for the treatment of diverse diseases such as metabolic syndromes and cancers owing to its anti-inflammatory, antioxidant, and anti-cancer effects [1,2]. In particular, recent studies have shown that Rg3 has excellent protective effects on skin cells against UV-induced aging via gene regulation including the reduction of matrix metalloprotease-1 and interleukin-6 gene expression, as well as increased collagen gene expression in skin fibroblasts and keratinocytes [3,4]. However, the biological benefits of Rg3 against photodamage by natural levels of infrared-A (IRA; wavelength of 700-1400 nm) irradiation without heat effects have not yet been studied in detail. ...
... This result indicated that the level of mitochondrial ROS was successfully reduced by Rg3(S) and Rg3/Lipo, which was similar to that in Cell without IRA irradiation. In previous studies, the antioxidant activity of Rg3 restored the mitochondrial membrane potential in UV-damaged fibroblasts [3,4]. In this study, we demonstrated that Rg3(S) and Rg3/Lipo show a promising decrease in mitochondrial ROS induced by IRA irradiation. ...
... The annexin V intensity in Cell, Lipo, Con, Rg3(S), and Rg3/Lipo was 7.3 ± 3.7, 7.6 ± 4.8, 16.5 ± 8.8, 3.5 ± 2.3, and 4.7 ± 2.3, respectively. According to a previous study, the UV-induced pro-apoptotic factor cytochrome-c was reduced by Rg3(S), which might be one of the potential mechanisms of decreased annexin V levels by Rg3/ Lipo [3,4]. ...
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Protection of skin cells from chronic infrared-A (IRA) irradiation is crucial for anti-photoaging of the skin. In this study, we investigated the protective activity of Rg3(S) and Rg3(S)-incorporated anionic soybean lecithin liposomes (Rg3/Lipo) with a size of approximately 150 nm against IRA-induced photodamage in human fibroblasts. The formulated Rg3/Lipo showed increased solubility in aqueous solution up to a concentration of 200 μg/ml, compared to free Rg3(S). In addition, Rg3/Lipo exhibited superior colloidal stability in aqueous solutions and biocompatibility for normal human dermal fibroblasts (NHDFs). After repeated IRA irradiation on NHDFs, elevated levels of cellular and mitochondrial reactive oxygen species (ROS) were greatly reduced by Rg3(S) and Rg3/Lipo. In addition, cells treated with Rg3/Lipo exhibited noticeably reduced apoptotic signals following IRA irradiation compared to untreated cells. Thus, considering aqueous solubility and cellular responses, Rg3/Lipo could serve as a promising infrared protector for healthy aging of skin cells.
... Ginsenoside Rg3 (Rg3) is one of the most important components from the traditional Chinese medicine Panax ginseng and has emerged as an effective anti-oxidative, antiinflammatory, anticancer, antifatiguing, and cardioprotective medicine with evident effects (Kao et al., 2020). Recently, the use of Rg3 in the skin has started gaining considerable research attention, and Rg3 is considered to have therapeutic benefits in malignant melanoma, atopic dermatitis, skin senescence, and skin healing (Shan et al., 2014;Lee et al., 2018Lee et al., , 2019. Moreover, several studies have suggested that Rg3 serves as an early intervention for treating patients with hypertrophic scars (HS) by promoting wound healing in the early stage and inhibiting scar hyperplasia in the late stage (Cheng et al., 2013;Sun et al., 2014;Xu et al., 2019). ...
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Ginsenoside Rg3 has shown beneficial effects in various skin diseases. The current interest in designing and developing hydrogels for biomedical applications continues to grow, inspiring the further development of drug-loaded hydrogels for tissue repair and localized drug delivery. The aim of the present study was to develop an effective and safe hydrogel (Rg3-Gel), using ginsenoside Rg3, and we evaluated the wound-healing potential and therapeutic mechanism of Rg3-Gel. The results indicated that the optimized Rg3-Gel underwent discontinuous phase transition at low and high temperatures. Rg3-Gel also exhibited good network structures, swelling water retention capacity, sustainable release performance, and excellent biocompatibility. Subsequently, the good antibacterial and antioxidant properties of Rg3-Gel were confirmed by in vitro tests. In full-thickness skin defect wounded models, Rg3-Gel significantly accelerated the wound contraction, promoted epithelial and tissue regeneration, and promoted collagen deposition and angiogenesis. In addition, Rg3-Gel increased the expression of autophagy proteins by inhibiting the MAPK and NF-KB pathways in vivo. It simultaneously regulated host immunity by increasing the abundance of beneficial bacteria and the diversity of the wound surface flora. From these preliminary evaluations, it is possible to conclude that Rg3-Gel has excellent application potential in wound-healing drug delivery systems.
... Moreover, several studies have shown that ginseng exerts a strong cardioprotective effect in cardiovascular diseases in vivo and ex vivo; which is reflected in ginseng medicine and ginseng extracts such as ginsenosides. In the animal model of myocardial ischemia-reperfusion injury, ginseng protected the heart through multiple signaling pathways, such as the nitric oxide (NO) signaling pathway, which improved vascular endothelial function and reduced apoptosis by anti-oxidation (Lee et al., 2019). In this study, we found that NXK, with red ginseng and Mao holly as the main components, exerted anti-inflammatory properties and inhibited the expression of inflammatory factors of CHF. ...
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Nuanxinkang tablet (NXK), a Chinese herbal formula, can improve heart function and quality of life in patients with chronic heart failure (CHF). However, the mechanisms of action of NXK are not fully understood. In this study, we investigated the effects of NXK on inflammation in the CHF mouse model. This model was established by transverse aortic constriction (TAC) and treated with NXK for 8 weeks. Then, the cardiac function and myocardial fibrosis were evaluated. The monocytes/macrophages were evaluated by immunofluorescence. The mRNA levels of IL-1β, IL-6, TNF-α, ICAM-1, and VCAM-1 were measured by quantitative real-time polymerase chain reaction (qRT-PCR), while TLR4, MyD88, NF-κB p65, P-IκBα, TLR2, TLR7 and TLR9 protein levels were evaluated by Western blot. The results showed that NXK improved the left ventricular ejection fraction (LVEF) and left ventricular end-systolic dimension, reversed myocardial fibrosis, and inhibited pro-inflammatory (CD11b + Ly6C+) monocytes/macrophages in the TAC mouse model. NXK also reduced the mRNA and protein levels of the above markers. Taken together, NXK improved heart function and reduced inflammation through the TLR-mediated NF-κB signaling pathway, suggesting that it might be used as an innovative treatment strategy for CHF.
... Recently, the rare minor ginsenosides have been proved to be more efficient active pharmacological agents compared with the major ginsenosides [17]. Accordingly, many rare ginsenosides such as Rg3 and C-Mx have been demonstrated pharmacological activities with regard to UVB-induced skin aging [18,19]. Until now, hundreds of rare ginsenosides have been identified. ...
Article
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Long-term exposure to ultraviolet light induces photoaging and may eventually increase the risk of skin carcinogenesis. Rare minor ginsenosides isolating from traditional medicine Panax (ginseng) have shown biomedical efficacy as antioxidation and antiphotodamage agents. However, due to the difficulty of component extraction and wide variety of ginsenoside, the identification of active antiphotoaging ginsenoside remains a huge challenge. In this study, we proposed a novel in silico approach to identify potential compound against photoaging from 82 ginsenosides. Specifically, we calculated the shortest distance between unknown and known antiphotoaging ginsenoside set in the chemical space and applied chemical structure similarity assessment, drug-likeness screening, and ADMET evaluation for the candidates. We highlighted three rare minor ginsenosides (C-Mc, Mx, and F2) that possess high potential as antiphotoaging agents. Among them, C-Mc deriving from American ginseng (Panax quinquefolius L.) was validated by wet-lab experimental assays and showed significant antioxidant and cytoprotective activity against UVB-induced photodamage in human dermal fibroblasts. Furthermore, system pharmacology analysis was conducted to explore the therapeutic targets and molecular mechanisms through integrating global drug-target network, high quality photoaging-related gene profile from multiomics data, and skin tissue-specific expression protein network. In combination with in vitro assays, we found that C-Mc suppressed MMP production through regulating the MAPK/AP-1/NF-κB pathway and expedited collagen synthesis via the TGF-β/Smad pathway, as well as enhanced the expression of Nrf2/ARE to hold a balance of endogenous oxidation. Overall, this study offers an effective drug discovery framework combining in silico prediction and in vitro validation, uncovering that ginsenoside C-Mc has potential antiphotoaging properties and might be a novel natural agent for use in oral drug, skincare products, or functional food.
... Cell viability assay were performed as previously described [24]. ...
... ROS assay was performed as previously described [24]. NHDF cells were plated and incubated at a density of 5 Â 10 5 cells/well in 6-well culture plates for 24 h. ...
... And NHDF cells were transfected the pDsRed2-Mito and GFP-LC3 plasmid using JetPEI reagents. Confocal analysis was performed as previously described [24,25]. ...
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Background In addition to its use as a health food, ginseng is used in cosmetics and shampoo because of its extensive health benefits. The ginsenoside, Rh2, is a component of ginseng that inhibits tumor cell proliferation and differentiation, promotes insulin secretion, improves insulin sensitivity, and shows antioxidant effects. Methods The effects of Rh2 on cell survival, extracellular matrix (ECM) protein expression, and cell differentiation were examined. The antioxidant effects of Rh2 in UV-irradiated normal human dermal fibroblast (NHDF) cells were also examined. The effects of Rh2 on mitochondrial function, morphology, and mitophagy were investigated in UV-irradiated NHDF cells. Results Rh2 treatment promoted the proliferation of NHDF cells. Additionally, Rh2 increased the expression levels of ECM proteins and growth-associated immediate-early genes in ultraviolet (UV)-irradiated NHDF cells. Rh2 also affected antioxidant protein expression and increased total antioxidant capacity. Furthermore, treatment with Rh2 ameliorated the changes in mitochondrial morphology, induced the recovery of mitochondrial function, and inhibited the initiation of mitophagy in UV-irradiated NHDF cells. Conclusion Rh2 inhibits mitophagy and reinstates mitochondrial ATP production and membrane potential in NHDF cells damaged by UV exposure, leading to the recovery of ECM, cell proliferation, and antioxidant capacity.
... Ginsenoside Rg3 is a tetracyclic triterpenoid saponin. Previous studies show that ginsenoside Rg3 possesses a good many of pharmacological activities, such as antioxidant (15) , anticancer (16) , cardiovascular protection (17) , immune improvement (18) , anti-inflammation (19) , and antiaging effects (20) . Ginsenoside Rg3 alleviates the dopaminergic nerve injury in Parkinson's disease mice through its antioxidant effects (21)(22) . ...
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Objectives: Acute lung injury is commonly found in patients with insecticide poisoning and the pathogenesis is related to oxidative stress. Ginsenoside Rg3, one of the main constituents of Panax ginseng C.A. Meyer, shows an anti-oxidative activity. The aim of this study was to evaluate whether ginsenoside Rg3 can alleviate lung injury induced by rotenone in mice. Methods: C57BL/6J male mice were divided into five groups (n=11). The mice in ginsenoside Rg3 groups were treated with ginsenoside Rg3 at dose of 5, 10 or 20 mg/kg. Except for the control group, mice were challenged intragastrically with rotenone at dose of 30 mg/kg, once a day for 6 weeks. Subsequently, the lung tissues of mice were collected. The effect of ginsenoside Rg3 on rotenone-induced lung injury was observed by hematoxylin and eosin staining. The oxidative stress in lung tissues were also examined. Results: Rotenone induced substantial hemorrhage, alveolar wall thickness and neutrophils infiltration. These structural damages were attenuated significantly by ginsenoside Rg3 treatment. The lung injury induced by rotenone was associated with oxidative stress in lung tissues of mice. Compared with the control group, rotenone exposure resulted in the increase of malondialdehyde (MDA), the decreases of the activities of superoxide dismutase (SOD), glutathione peroxidase (GHS-Px), and the glutathione (GSH) content. Nevertheless, ginsenoside Rg3 treatment not only reduced MDA production but also increased the activities of SOD, GSH-Px, and the content of GSH in lung tissue of mice. Conclusion: Taken together, this study demonstrated that ginsenoside Rg3 has potential to ameliorate rotenone-induced lung injury and the mechanism of action of ginsenoside Rg3 is mediated by its anti-oxidative properties.