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Chinese tonifying herbs, which are classified into four functional categories (namely, Yang, Qi, Yin, Blood) are commonly used for restoring normal body function and the prevention of diseases. To explore cell-based biological markers for Blood-enriching Chinese herbs, we investigate the effect of 11 commonly used Blood-enriching herbs on erythropoietin (EPO) production in HepG2 cells. Herbs for nourishing Yin were tested for determining the specificity of Blood-enriching herbs in inducing EPO production. In addition, the effects of Blood-enriching herbs on nitric oxide (NO) production in both HepG2 cells and human umbilical vein endothelial cells (HUVECs) were also investigated. The results indicated that methanolic extracts of Blood-enriching herbs (but not Yin-nourishing herbs) showed characteristic pharmacological activity in inducing EPO production in HepG2 cells and NO release in HUVECs. The experimental findings, therefore, support the use of cell-based EPO production and NO release as biological markers for Blood-enriching Chinese tonifying herbs.

The present study investigated the effect of treatment with methanolic extracts of Yin- and Yang-Chinese tonifying herbs on concanavalin A (Con A)/lipopolysaccharide (LPS)-stimulated splenocyte proliferation (adaptive immunity) and natural killer (NK) cell activity (innate immunity) in an ex vivo mouse model. The results indicated that while treatment with most Yin herbal extracts potentiated the Con A/LPS-stimulated splenocyte proliferation, only Yang (but not Yin) herbal extracts stimulated NK cell activity. The differential effects of Yin- and Yang-Chinese tonifying herbs on innate and adaptive immunity are consistent with the Chinese medicine theory which depicts the Yin and Yang functional components of Zheng Qi (vital energy), with the Yang component being responsible for the first line of defense against invading microorganisms (i.e., innate immunity) and the Yin oner serving as a follow-up defensive response (adaptive immunity).

Background Diabetic kidney disease (DKD) is one of the major chronic microvascular complications of diabetes and the main cause of end-stage renal failure. Zhenwu Decoction (ZWD), an ancient classic herbal formula in Chinese medicine, has been clinically used for the treatment of kidney disease in China for many years. However, there is currently limited research investigating the application of ZWD in the treatment of DKD and the underlying chemical and biochemical mechanisms involved. Therefore, in the present study, we aimed to identify active components in ZWD and unravel the possible mechanism(s) of action for ZWD in treating DKD. Methods The protective effect of ZWD against DKD was evaluated utilizing an in vitro model of diabetic renal proximal tubulopathy. The major chemical components from ZWD were identified by LC-MS/MS. Drug targets were predicted by submitting the SMILES (Simplified Molecular Input Line Entry System) of the compounds to SEA (Similarity Ensemble Approach) search server and SwissTargetPrediction. The differentially expressed genes (DEGs) of the disease were collected and integrated from GeneCards. The constructions of “Compounds-potential targets interaction” (CTI) network and Protein-Protein Interaction (PPI) network, as well as topology analysis were conducted by Cytoscape. Gene Ontology (GO) enrichment and Metacore pathway enrichment analysis were also performed. Lastly, molecular docking and experimental studies were adopted to validate the core target and identify an active component(s) of ZWD. Results We demonstrated that the ZWD extract could significantly rescue the palmitic acid (PA) and high glucose-induced apoptotic cell death in HK-2 cells, and the cytoprotection was accompanied by decreases in the extent of reactive oxygen species (ROS) production, mitochondrial membrane depolarization and ATP depletion. Fifty-seven compounds in the aqueous extract of ZWD were identified by LC-MS. The results of PPI analysis showed that top hu

The present study investigated the effect of an herbal extract-supplemented cardiomyopeptin preparation (HECP), in the rat model of chronic heart failure. HECP pre-/co-treatment at a daily dose of 0.072 to 0.124 g/kg for 30 days protected against isoproterenol (ISO)-induced chronic myocardial damage in rats in a dose-dependent manner, with the extent of protection, as assessed by plasma cardiac troponin I level, being up to 76%. The cardioprotection afforded by HECP was associated with the enhancement of myocardial mitochondrial antioxidant status, amelioration of plasma parameters on cardiac dysfunction and hypertrophy, as well as an increase in myocardial endothelial nitric oxide synthase activity. Myocardial apoptotic and anti-apoptotic parameters were suppressed and stimulated, respectively. The cardioprotection afforded by HECP was accompanied by an increase in exercise capacity, an indirect functional index of the myocardium, in ISO-challenged rats. In conclusion, HECP may offer a promising prospect in preventing chronic heart failure in human subjects.

Background: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality. Mitochondrial dysfunction has been implicated as a key factor in the development of CKD. According to traditional Chinese medicine (TCM) theory, many Chinese Yang/Qi-invigorating botanical drugs/herbal formulations have been shown to produce promising outcomes in the clinical management of CKD. Experimental studies have indicated that the health-promoting action of Yang/Qi invigoration in TCM is related to the up-regulation of mitochondrial energy generation and antioxidant status. Objective: In this review, we aim to test whether Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations can provide medical benefits in CKD and its complications. And we also explore the possible involvement of mitochondrial-associated signaling pathway underlying the beneficial effects of Yang/Qi invigoration in TCM. Methods: A systematic search of “PubMed”, “China National Knowledge Infrastructure (CNKI)” and “Google Scholar” was carried out to collect all the available articles in English or Chinese related to Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations and their effects on mitochondrial function and chronic kidney disease. Result and Discussion: The relationship between the progression of CKD and mitochondrial function is discussed. The effects of Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations and their active ingredients, including phytosterols/triterpenes, flavonoids, and dibenzocyclooctadiene lignans, on CKD and related alterations in mitochondrial signaling pathways are also presented in this review. In the future, exploration of the possible beneficial effects and clinical studies of more Yang- and Qi-invigorating botanical drugs/herbal formulations in the prevention and/or/treatment of CKD and the molecular mechanisms relating to the enhancement of mitochondrial functions warrants further investigation. Conclusion: Given the

Cordyceps mycelium extract (Cs-4), Chicken Essence (CE), and their combination were investigated for antioxidant and immunomodulatory activities in mouse models. Long-term treatment with Cs-4 or CE at equivalent human doses improved antioxidant status in various tissues, as evidenced by the enhancement of mitochondrial glutathione redox status in the brain, liver, heart, and kidney of mice. Cs-4 or CE treatment also produced an immunomodulatory action, as indicated by the potentiation of Concanavalin A-/lipopolysaccharide-induced proliferation of mouse splenocytes ex vivo. While doubling of the equivalent human doses of Cs-4 and CE did not further enhance their antioxidant or immunopotentiating effects, the combined treatment with Cs-4 and CE at their respective equivalent human doses produced an additive effect, with the extents of stimulation being larger than those produced by Cs-4 or CE alone. The results have demonstrated for the first time that the combined use of Cs-4 and CE can produce an additive effect on both antioxidation and immunopotentiation that cannot otherwise be achieved by increasing the equivalent human doses of Cs-4 or CE alone.

Schisandrae Fructus (SF), the fruit of Schisandra chinensis (Turcz.) Baillon, has been used for the treatment of liver injury and metabolism-related disorders in China. The objective of this study was to investigate the effects of supplementation with ethanol extract of SF seed (EtSF-S) on serum/hepatic lipid and glucose levels as well as fecal total cholesterol (TC) contents in mice fed a normal diet (ND) or high-fat/fructose diet (HFFD) containing 15% lard oil and 15% fructose. Female ICR mice (18-20 gin body weight) were fed with ND or HFFD for 3 months, and then EtSF-S was added to both chow diets at increasing concentrations of 1, 5, and 10% (w/w). Thirty days later, serum and hepatic lipids, including TC, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and glucose, were measured. Dietary supplementation with EtSF-S reduced hepatic TC (36 and 18%) and TG levels (38 and 28%) and increased serum HDL/LDL ratio (16 and 26%) in both ND- and HFFD-fed mice, respectively. Moreover, supplementation with EtSF-S elevated serum HDL (31%) in HFFD-fed mice and reduced serum LDL (27%) in ND-fed mice. EtSF-S treatment reduced fat mass (40%) in ND-fed mice and increased fecal TC contents (33%) in HFFD-fed mice. EtSF-S supplementation decreased hepatic glucose contents (29%) in both ND- and HFFD-fed mice. However, diet supplemented with EtSF-S elevated serum TG levels (up to 123%) and hepatic size (28%), but more importantly, suppressed the body weight gain (approximately 130%) in mice fed with HFFD. These findings suggested that dietary supplementation with EtSF-S as natural herbal function food may be a useful strategy for the treatment of patients with fatty liver disease or overweight without a high intake of sugar and fat.

In the present study, two cell-based systems for assessing Yang and Yin activities were for the first time used to investigate the effect of ursolic acid (UA) and oleanolic acid (OA). The results indicated that while UA was only active in the Yang assay, OA produced activity in the Yin assay. The Yang/Yin activity of UA/OA may be attributed to their distinct molecular structures, which confer their differential ability to interact with mitochondrial membrane or cellular membrane lipids, with resultant membrane fluidization and potentiation of biological responses.

Background: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality. Mitochondrial dysfunction has been implicated as a key factor in the development of CKD. According to traditional Chinese medicine (TCM) theory, many Chinese Yang/Qi-invigorating botanical drugs/herbal formulations have been shown to produce promising outcomes in the clinical management of CKD. Experimental studies have indicated that the health-promoting action of Yang/Qi invigoration in TCM is related to the up-regulation of mitochondrial energy generation and antioxidant status. Objective: In this review, we aim to test whether Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations can provide medical benefits in CKD and its complications. And we also explore the possible involvement of mitochondrial-associated signaling pathway underlying the beneficial effects of Yang/Qi invigoration in TCM. Methods: A systematic search of “PubMed”, “China National Knowledge Infrastructure (CNKI)” and “Google Scholar” was carried out to collect all the available articles in English or Chinese related to Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations and their effects on mitochondrial function and chronic kidney disease. Result and Discussion: The relationship between the progression of CKD and mitochondrial function is discussed. The effects of Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations and their active ingredients, including phytosterols/triterpenes, flavonoids, and dibenzocyclooctadiene lignans, on CKD and related alterations in mitochondrial signaling pathways are also presented in this review. In the future, exploration of the possible beneficial effects and clinical studies of more Yang- and Qi-invigorating botanical drugs/herbal formulations in the prevention and/or/treatment of CKD and the molecular mechanisms relating to the enhancement of mitochondrial functions warrants further investigation. Conclusion: Given the

Schisandrae Fructus (SF), the fruit of Schisandra chinensis (Turcz.) Baillon, has been used for the treatment of liver injury and metabolism-related disorders in China. The objective of this study was to investigate the effects of supplementation with ethanol extract of SF seed (EtSF-S) on serum/hepatic lipid and glucose levels as well as fecal total cholesterol (TC) contents in mice fed a normal diet (ND) or high-fat/fructose diet (HFFD) containing 15% lard oil and 15% fructose. Female ICR mice (18-20 gin body weight) were fed with ND or HFFD for 3 months, and then EtSF-S was added to both chow diets at increasing concentrations of 1, 5, and 10% (w/w). Thirty days later, serum and hepatic lipids, including TC, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and glucose, were measured. Dietary supplementation with EtSF-S reduced hepatic TC (36 and 18%) and TG levels (38 and 28%) and increased serum HDL/LDL ratio (16 and 26%) in both ND- and HFFD-fed mice, respectively. Moreover, supplementation with EtSF-S elevated serum HDL (31%) in HFFD-fed mice and reduced serum LDL (27%) in ND-fed mice. EtSF-S treatment reduced fat mass (40%) in ND-fed mice and increased fecal TC contents (33%) in HFFD-fed mice. EtSF-S supplementation decreased hepatic glucose contents (29%) in both ND- and HFFD-fed mice. However, diet supplemented with EtSF-S elevated serum TG levels (up to 123%) and hepatic size (28%), but more importantly, suppressed the body weight gain (approximately 130%) in mice fed with HFFD. These findings suggested that dietary supplementation with EtSF-S as natural herbal function food may be a useful strategy for the treatment of patients with fatty liver disease or overweight without a high intake of sugar and fat.

Cordyceps mycelium extract (Cs-4), Chicken Essence (CE), and their combination were investigated for antioxidant and immunomodulatory activities in mouse models. Long-term treatment with Cs-4 or CE at equivalent human doses improved antioxidant status in various tissues, as evidenced by the enhancement of mitochondrial glutathione redox status in the brain, liver, heart, and kidney of mice. Cs-4 or CE treatment also produced an immunomodulatory action, as indicated by the potentiation of Concanavalin A-/lipopolysaccharide-induced proliferation of mouse splenocytes ex vivo. While doubling of the equivalent human doses of Cs-4 and CE did not further enhance their antioxidant or immunopotentiating effects, the combined treatment with Cs-4 and CE at their respective equivalent human doses produced an additive effect, with the extents of stimulation being larger than those produced by Cs-4 or CE alone. The results have demonstrated for the first time that the combined use of Cs-4 and CE can produce an additive effect on both antioxidation and immunopotentiation that cannot otherwise be achieved by increasing the equivalent human doses of Cs-4 or CE alone.

In the present study, two cell-based systems for assessing Yang and Yin activities were for the first time used to investigate the effect of ursolic acid (UA) and oleanolic acid (OA). The results indicated that while UA was only active in the Yang assay, OA produced activity in the Yin assay. The Yang/Yin activity of UA/OA may be attributed to their distinct molecular structures, which confer their differential ability to interact with mitochondrial membrane or cellular membrane lipids, with resultant membrane fluidization and potentiation of biological responses.

Cordyceps mycelium extract (Cs-4), Chicken Essence (CE), and their combination were investigated for antioxidant and immunomodulatory activities in mouse models. Long-term treatment with Cs-4 or CE at equivalent human doses improved antioxidant status in various tissues, as evidenced by the enhancement of mitochondrial glutathione redox status in the brain, liver, heart, and kidney of mice. Cs-4 or CE treatment also produced an immunomodulatory action, as indicated by the potentiation of Concanavalin A-/lipopolysaccharide-induced proliferation of mouse splenocytes ex vivo. While doubling of the equivalent human doses of Cs-4 and CE did not further enhance their antioxidant or immunopotentiating effects, the combined treatment with Cs-4 and CE at their respective equivalent human doses produced an additive effect, with the extents of stimulation being larger than those produced by Cs-4 or CE alone. The results have demonstrated for the first time that the combined use of Cs-4 and CE can produce an additive effect on both antioxidation and immunopotentiation that cannot otherwise be achieved by increasing the equivalent human doses of Cs-4 or CE alone.

Background: Chronic kidney disease (CKD) is a leading cause of morbidity and mortality. Mitochondrial dysfunction has been implicated as a key factor in the development of CKD. According to traditional Chinese medicine (TCM) theory, many Chinese Yang/Qi-invigorating botanical drugs/herbal formulations have been shown to produce promising outcomes in the clinical management of CKD. Experimental studies have indicated that the health-promoting action of Yang/Qi invigoration in TCM is related to the up-regulation of mitochondrial energy generation and antioxidant status. Objective: In this review, we aim to test whether Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations can provide medical benefits in CKD and its complications. And we also explore the possible involvement of mitochondrial-associated signaling pathway underlying the beneficial effects of Yang/Qi invigoration in TCM. Methods: A systematic search of “PubMed”, “China National Knowledge Infrastructure (CNKI)” and “Google Scholar” was carried out to collect all the available articles in English or Chinese related to Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations and their effects on mitochondrial function and chronic kidney disease. Result and Discussion: The relationship between the progression of CKD and mitochondrial function is discussed. The effects of Chinese Yang/Qi-invigorating tonic botanical drugs/herbal formulations and their active ingredients, including phytosterols/triterpenes, flavonoids, and dibenzocyclooctadiene lignans, on CKD and related alterations in mitochondrial signaling pathways are also presented in this review. In the future, exploration of the possible beneficial effects and clinical studies of more Yang- and Qi-invigorating botanical drugs/herbal formulations in the prevention and/or/treatment of CKD and the molecular mechanisms relating to the enhancement of mitochondrial functions warrants further investigation. Conclusion: Given the

Schisandrae Fructus (SF), the fruit of Schisandra chinensis (Turcz.) Baillon, has been used for the treatment of liver injury and metabolism-related disorders in China. The objective of this study was to investigate the effects of supplementation with ethanol extract of SF seed (EtSF-S) on serum/hepatic lipid and glucose levels as well as fecal total cholesterol (TC) contents in mice fed a normal diet (ND) or high-fat/fructose diet (HFFD) containing 15% lard oil and 15% fructose. Female ICR mice (18-20 gin body weight) were fed with ND or HFFD for 3 months, and then EtSF-S was added to both chow diets at increasing concentrations of 1, 5, and 10% (w/w). Thirty days later, serum and hepatic lipids, including TC, triglyceride (TG), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and glucose, were measured. Dietary supplementation with EtSF-S reduced hepatic TC (36 and 18%) and TG levels (38 and 28%) and increased serum HDL/LDL ratio (16 and 26%) in both ND- and HFFD-fed mice, respectively. Moreover, supplementation with EtSF-S elevated serum HDL (31%) in HFFD-fed mice and reduced serum LDL (27%) in ND-fed mice. EtSF-S treatment reduced fat mass (40%) in ND-fed mice and increased fecal TC contents (33%) in HFFD-fed mice. EtSF-S supplementation decreased hepatic glucose contents (29%) in both ND- and HFFD-fed mice. However, diet supplemented with EtSF-S elevated serum TG levels (up to 123%) and hepatic size (28%), but more importantly, suppressed the body weight gain (approximately 130%) in mice fed with HFFD. These findings suggested that dietary supplementation with EtSF-S as natural herbal function food may be a useful strategy for the treatment of patients with fatty liver disease or overweight without a high intake of sugar and fat.

Corylin is a naturally occurring flavonoid isolated from the fruit of Psoralea corylifolia L. (Fabaceae), which is a Chinese medicinal herb in treating osteoporosis. Although a variety of pharmacological activities of corylin have been reported, its osteogenic action and the underlying mechanism in bone development remain unclear. In the present study, the involvement of bone-specific genes in corylininduced differentiated osteoblasts was analyzed by RT-PCR, promoter-reporter assay, and Western blotting. In cultured osteoblasts, corylin-induced cell differentiation and mineralization, as well as increased the expressions of vital biological markers for osteogenesis, such as Runx2, Osterix, Col1, and ALP. Corylin was proposed to have dual pathways in triggering the osteoblastic differentiation. First, the osteogenic function of corylin acted through the activation of Wnt/β-catenin signaling. The nuclear translocation of β-catenin of cultured osteoblasts, as determined by flow cytometry and confocal microscopy, was triggered by applied corylin, and which was blocked by DKK-1, an inhibitor of Wnt/β-catenin signaling. Second, the application of corylin-induced estrogenic response in a dose-dependent manner, and which was blocked by ICI 182 780, an antagonist of estrogen receptor. Furthermore, the activation of Runx2 promoter by corylin was abolished by both DKK-1 and ICI 182,780, indicating that the corylin exhibited its osteogenic effect via estrogen and Wnt/β-catenin signaling pathways. In addition, corylin regulated the metabolic profiles, as well as the membrane potential of mitochondria, in cultured osteoblasts. Corylin also stimulated the osteogenesis in bone micromass derived from mesenchymal progenitor cells. This study demonstrated the osteogenic activities of corylin in osteoblasts and micromass, suggesting that corylin has the potential to be developed as a novel pro-osteogenic agent in targeting for the treatment of osteoblast-mediated osteoporosis. © 2020 F

Allergic rhinitis and asthma are common chronic allergic diseases of the respiratory tract, which are accompanied by immunoglobulin E (IgE)-mediated inflammation and the involvement of type 2 T helper cells, mast cells, and eosinophils. Cordyceps sinensis (Berk.) Sacc is a fungal parasite on the larva of Lepidoptera. It has been considered to be a health-promoting food and, also, one of the best-known herbal remedies for the treatment of airway diseases, such as asthma and lung inflammation. In the present study, we demonstrated the antiallergic rhinitis effect of Cs-4, a water extract prepared from the mycelium culture of Cordyceps sinensis (Berk) Sacc, on ovalbumin (OVA)-induced allergic rhinitis in mice and the anti-asthmatic effect of Cs-4 in a rat model of asthma. Treatment with Cs-4 suppressed the nasal symptoms induced in OVA-sensitized and challenged mice. The inhibition was associated with a reduction in IgE/OVA-IgE and interleukin (IL)-4/IL-13 levels in the nasal fluid. Cs-4 treatment also decreased airway responsiveness and ameliorated the scratching behavior in capsaicin-challenged rats. It also reduced plasma IgE levels, as well as IgE and eosinophil peroxidase levels, in the bronchoalveolar fluid. Cs-4 treatment completely suppressed the increases in IL-4, IL-5, and IL-13 levels in rat lung tissue. In conclusion, our results suggest that Cs-4 has the potential to alleviate immune hypersensitivity reactions in allergic rhinitis and asthma. © 2020 by the authors.

Allergic rhinitis and asthma are common chronic allergic diseases of the respiratory tract, which are accompanied by immunoglobulin E (IgE)-mediated inflammation and the involvement of type 2 T helper cells, mast cells, and eosinophils. Cordyceps sinensis (Berk.) Sacc is a fungal parasite on the larva of Lepidoptera. It has been considered to be a health-promoting food and, also, one of the best-known herbal remedies for the treatment of airway diseases, such as asthma and lung inflammation. In the present study, we demonstrated the antiallergic rhinitis effect of Cs-4, a water extract prepared from the mycelium culture of Cordyceps sinensis (Berk) Sacc, on ovalbumin (OVA)-induced allergic rhinitis in mice and the anti-asthmatic effect of Cs-4 in a rat model of asthma. Treatment with Cs-4 suppressed the nasal symptoms induced in OVA-sensitized and challenged mice. The inhibition was associated with a reduction in IgE/OVA-IgE and interleukin (IL)-4/IL-13 levels in the nasal fluid. Cs-4 treatment also decreased airway responsiveness and ameliorated the scratching behavior in capsaicin-challenged rats. It also reduced plasma IgE levels, as well as IgE and eosinophil peroxidase levels, in the bronchoalveolar fluid. Cs-4 treatment completely suppressed the increases in IL-4, IL-5, and IL-13 levels in rat lung tissue. In conclusion, our results suggest that Cs-4 has the potential to alleviate immune hypersensitivity reactions in allergic rhinitis and asthma. © 2020 by the authors.

Allergic rhinitis and asthma are common chronic allergic diseases of the respiratory tract, which are accompanied by immunoglobulin E (IgE)-mediated inflammation and the involvement of type 2 T helper cells, mast cells, and eosinophils. Cordyceps sinensis (Berk.) Sacc is a fungal parasite on the larva of Lepidoptera. It has been considered to be a health-promoting food and, also, one of the best-known herbal remedies for the treatment of airway diseases, such as asthma and lung inflammation. In the present study, we demonstrated the antiallergic rhinitis effect of Cs-4, a water extract prepared from the mycelium culture of Cordyceps sinensis (Berk) Sacc, on ovalbumin (OVA)-induced allergic rhinitis in mice and the anti-asthmatic effect of Cs-4 in a rat model of asthma. Treatment with Cs-4 suppressed the nasal symptoms induced in OVA-sensitized and challenged mice. The inhibition was associated with a reduction in IgE/OVA-IgE and interleukin (IL)-4/IL-13 levels in the nasal fluid. Cs-4 treatment also decreased airway responsiveness and ameliorated the scratching behavior in capsaicin-challenged rats. It also reduced plasma IgE levels, as well as IgE and eosinophil peroxidase levels, in the bronchoalveolar fluid. Cs-4 treatment completely suppressed the increases in IL-4, IL-5, and IL-13 levels in rat lung tissue. In conclusion, our results suggest that Cs-4 has the potential to alleviate immune hypersensitivity reactions in allergic rhinitis and asthma. © 2020 by the authors.

Xiao-Er-An-Shen Decoction (XEASD) has been used clinically for the treatment of Tourette syndrome (TS) in children for more than 20 years in mainland China. The biochemical mechanism underlying the therapeutic action produced by XEASD treatment against TS remains unknown. However, a previous study has shown that pre-incubation of PC12 neuronal cells with XEASD can induce neurite outgrowth and protect against oxidative stress. In the present study, using a mouse model of TS induced by 3,3'-iminodipropionitrile (IDPN), stereotypy scoring, and locomotor activity were assessed. Levels of neurotransmitters including glutamate, aspartate, and gamma-aminobutyric acid (GABA) in brain tissue as well as plasma cyclic adenosine monophosphate (cAMP) were measured using assay kits. The ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) and Mn-superoxide dismutase (MnSOD) activity in brain mitochondrial fractions as well as mitochondrial glutathione reductase and cytosolic gamma-glutamylcysteine activities were also examined. The phosphorylation of cAMP-responsive element binding protein (CREB) in brain tissue was measured by Western blot analysis. XEASD treatment was found to significantly ameliorate the severity of behavioral symptoms in affected mice, as evidenced by decreases in the stereotypy score and locomotor activity. The beneficial effect of XEASD was accompanied by the reversal of abnormal levels of GABA, glutamate, and aspartate, in brain tissue of IDPN-challenged mice. In addition, XEASD treatment increased plasma cyclic adenosine monophosphate (cAMP) levels and activated the phosphorylation of CREB in brain tissue of TS mice. Furthermore, XEASD treatment was found to enhance the antioxidant status of brain tissue in affected mice, as evidenced by increases in the GSH/GSSG ratio and the activity of MnSOD in brain mitochondrial fractions. Taken together, these experimental results will hopefully provide insight into the pharmacological basis for the benefi

Xiao-Er-An-Shen Decoction (XEASD) has been used clinically for the treatment of Tourette syndrome (TS) in children for more than 20 years in mainland China. The biochemical mechanism underlying the therapeutic action produced by XEASD treatment against TS remains unknown. However, a previous study has shown that pre-incubation of PC12 neuronal cells with XEASD can induce neurite outgrowth and protect against oxidative stress. In the present study, using a mouse model of TS induced by 3,3'-iminodipropionitrile (IDPN), stereotypy scoring, and locomotor activity were assessed. Levels of neurotransmitters including glutamate, aspartate, and gamma-aminobutyric acid (GABA) in brain tissue as well as plasma cyclic adenosine monophosphate (cAMP) were measured using assay kits. The ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) and Mn-superoxide dismutase (MnSOD) activity in brain mitochondrial fractions as well as mitochondrial glutathione reductase and cytosolic gamma-glutamylcysteine activities were also examined. The phosphorylation of cAMP-responsive element binding protein (CREB) in brain tissue was measured by Western blot analysis. XEASD treatment was found to significantly ameliorate the severity of behavioral symptoms in affected mice, as evidenced by decreases in the stereotypy score and locomotor activity. The beneficial effect of XEASD was accompanied by the reversal of abnormal levels of GABA, glutamate, and aspartate, in brain tissue of IDPN-challenged mice. In addition, XEASD treatment increased plasma cyclic adenosine monophosphate (cAMP) levels and activated the phosphorylation of CREB in brain tissue of TS mice. Furthermore, XEASD treatment was found to enhance the antioxidant status of brain tissue in affected mice, as evidenced by increases in the GSH/GSSG ratio and the activity of MnSOD in brain mitochondrial fractions. Taken together, these experimental results will hopefully provide insight into the pharmacological basis for the benefi

Traditional Chinese medicine views the human body as an organic entity made of various organs that function in a mutually interdependent manner. Pharmacological investigations of Chinese tonifying herbs have demonstrated that Yang/Qi-invigorating herbs can increase mitochondrial ATP generation capacity, whereas Yin/Blood-tonifying herbs can produce immunomodulatory effects and/or enhance the production of red blood cells. The use of Chinese tonifying herbs and herbal products for preventive health has become increasingly popular throughout the world. Herbal products have been increasingly accepted and utilised in the United States for disease prevention and auxiliary treatment. Botanical authentication refers to the comparison between the herbal sample under consideration and an authenticated reference specimen. The evaluation of the quality of Chinese herbs presents a number of difficulties and challenges because of their unique modes of action and complex chemical composition. Chinese tonifying herbs and herbal health products can be classified into four functional categories: Yang-invigorating, Qi-invigorating, Yin-nourishing and Blood-enriching.

Xiao-Er-An-Shen Decoction (XEASD) has been used clinically for the treatment of Tourette syndrome (TS) in children for more than 20 years in mainland China. The biochemical mechanism underlying the therapeutic action produced by XEASD treatment against TS remains unknown. However, a previous study has shown that pre-incubation of PC12 neuronal cells with XEASD can induce neurite outgrowth and protect against oxidative stress. In the present study, using a mouse model of TS induced by 3,3'-iminodipropionitrile (IDPN), stereotypy scoring, and locomotor activity were assessed. Levels of neurotransmitters including glutamate, aspartate, and gamma-aminobutyric acid (GABA) in brain tissue as well as plasma cyclic adenosine monophosphate (cAMP) were measured using assay kits. The ratio of reduced glutathione (GSH)/oxidized glutathione (GSSG) and Mn-superoxide dismutase (MnSOD) activity in brain mitochondrial fractions as well as mitochondrial glutathione reductase and cytosolic gamma-glutamylcysteine activities were also examined. The phosphorylation of cAMP-responsive element binding protein (CREB) in brain tissue was measured by Western blot analysis. XEASD treatment was found to significantly ameliorate the severity of behavioral symptoms in affected mice, as evidenced by decreases in the stereotypy score and locomotor activity. The beneficial effect of XEASD was accompanied by the reversal of abnormal levels of GABA, glutamate, and aspartate, in brain tissue of IDPN-challenged mice. In addition, XEASD treatment increased plasma cyclic adenosine monophosphate (cAMP) levels and activated the phosphorylation of CREB in brain tissue of TS mice. Furthermore, XEASD treatment was found to enhance the antioxidant status of brain tissue in affected mice, as evidenced by increases in the GSH/GSSG ratio and the activity of MnSOD in brain mitochondrial fractions. Taken together, these experimental results will hopefully provide insight into the pharmacological basis for the benefi

8th Day superoxide dismutase (SOD)-Like Supreme (SOD-Like Supreme, a free radical scavenging health product) is an antioxidant-enriched fermentation preparation with free radical scavenging properties. In the present study, the cellular/tissue protective actions of SOD-Like Supreme against menadione toxicity in cultured H9c2 cardiomyocytes and in AML12 hepatocytes as well as oxidant-induced injury in the mouse myocardium and liver were investigated. SOD-Like Supreme was found to possess potent free radical scavenging activity in vitro as assessed by an oxygen radical absorbance capacity assay. Incubation with SOD-Like Supreme (0.5–3% (v/v)) was shown to protect against menadione-induced toxicity in H9c2 and AML12 cells, as evidenced by increases in cell viability. The ability of SOD-Like Supreme to protect against menadione cytotoxicity was associated with an elevation in the cellular reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio in menadione-challenged cells. Consistent with the cell-based studies, pre-/post-treatment with SOD-Like Supreme (0.69 and 2.06 mL/kg, three intermittent doses per day for two consecutive days) was found to protect against isoproterenol-induced myocardial injury and carbon tetrachloride hepatotoxicity in mice. The cardio/hepatoprotection afforded by SOD-Like Supreme was also paralleled by increases in myocardial/hepatic mitochondrial GSH/GSSG ratios in the SOD-Like Supreme-treated/oxidant-challenged mice. In conclusion, incubation/treatment with SOD-Like Supreme was found to protect against oxidant-induced injury in vitro and in vivo, presumably by virtue of its free radical scavenging activity. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.

8th Day superoxide dismutase (SOD)-Like Supreme (SOD-Like Supreme, a free radical scavenging health product) is an antioxidant-enriched fermentation preparation with free radical scavenging properties. In the present study, the cellular/tissue protective actions of SOD-Like Supreme against menadione toxicity in cultured H9c2 cardiomyocytes and in AML12 hepatocytes as well as oxidant-induced injury in the mouse myocardium and liver were investigated. SOD-Like Supreme was found to possess potent free radical scavenging activity in vitro as assessed by an oxygen radical absorbance capacity assay. Incubation with SOD-Like Supreme (0.5–3% (v/v)) was shown to protect against menadione-induced toxicity in H9c2 and AML12 cells, as evidenced by increases in cell viability. The ability of SOD-Like Supreme to protect against menadione cytotoxicity was associated with an elevation in the cellular reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio in menadione-challenged cells. Consistent with the cell-based studies, pre-/post-treatment with SOD-Like Supreme (0.69 and 2.06 mL/kg, three intermittent doses per day for two consecutive days) was found to protect against isoproterenol-induced myocardial injury and carbon tetrachloride hepatotoxicity in mice. The cardio/hepatoprotection afforded by SOD-Like Supreme was also paralleled by increases in myocardial/hepatic mitochondrial GSH/GSSG ratios in the SOD-Like Supreme-treated/oxidant-challenged mice. In conclusion, incubation/treatment with SOD-Like Supreme was found to protect against oxidant-induced injury in vitro and in vivo, presumably by virtue of its free radical scavenging activity. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.

8th Day superoxide dismutase (SOD)-Like Supreme (SOD-Like Supreme, a free radical scavenging health product) is an antioxidant-enriched fermentation preparation with free radical scavenging properties. In the present study, the cellular/tissue protective actions of SOD-Like Supreme against menadione toxicity in cultured H9c2 cardiomyocytes and in AML12 hepatocytes as well as oxidant-induced injury in the mouse myocardium and liver were investigated. SOD-Like Supreme was found to possess potent free radical scavenging activity in vitro as assessed by an oxygen radical absorbance capacity assay. Incubation with SOD-Like Supreme (0.5–3% (v/v)) was shown to protect against menadione-induced toxicity in H9c2 and AML12 cells, as evidenced by increases in cell viability. The ability of SOD-Like Supreme to protect against menadione cytotoxicity was associated with an elevation in the cellular reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio in menadione-challenged cells. Consistent with the cell-based studies, pre-/post-treatment with SOD-Like Supreme (0.69 and 2.06 mL/kg, three intermittent doses per day for two consecutive days) was found to protect against isoproterenol-induced myocardial injury and carbon tetrachloride hepatotoxicity in mice. The cardio/hepatoprotection afforded by SOD-Like Supreme was also paralleled by increases in myocardial/hepatic mitochondrial GSH/GSSG ratios in the SOD-Like Supreme-treated/oxidant-challenged mice. In conclusion, incubation/treatment with SOD-Like Supreme was found to protect against oxidant-induced injury in vitro and in vivo, presumably by virtue of its free radical scavenging activity. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.

Schisandrin A (Sch A) and schisandrin B (Sch B) are active components of Schisandrae Fructus. We compared the biochemical mechanism underlying the anti-inflammatory action of Sch A and Sch B, using cultured lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and concanavalin (ConA)-stimulated mouse splenocytes. Pre-incubation with Sch A or Sch B produced an anti-inflammatory action in LPS-stimulated RAW264.7 cells, as evidenced by the inhibition of the pro-inflammatory c-Jun N-terminal kinases/p38 kinase/nuclear factor-kappa B signaling pathway as well as the suppression of various pro-inflammatory cytokines and effectors, with the extent of inhibition by Sch A being more pronounced. The greater activity of Sch A in anti-inflammatory response was associated with a greater decrease in cellular reduced glutathione (GSH) level and a greater increase in glutathione S-transferase activity than corresponding changes produced by Sch B. However, upon incubation, only Sch B resulted in the activation of the nuclear factor (erythroid-derived 2)-like factor 2 and the induction of a significant increase in the expression of thioredoxin (TRX) in RAW264.7 cells. The Sch B-induced increase in TRX expression was associated with the suppression of pro-inflammatory cytokines and effectors in LPS-stimulated macrophages. Studies in a mouse model of inflammation (carrageenan-induced paw edema) indicated that while long-term treatment with either Sch A or Sch B suppressed the extent of paw edema, only acute treatment with Sch A produced a significant degree of inhibition on the inflammatory response. Although only Sch A decreased the cellular GSH level and suppressed the release of pro-inflammatory cytokines and cell proliferation in ConA-simulated splenocytes in vitro, both Sch A and Sch B treatments, while not altering cellular GSH levels, suppressed ConA-stimulated splenocyte proliferation ex vivo. These results suggest that Sch A and Sch B may act differentially on activating GS

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver lesions ranging from hepatic steatosis, nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. The high global prevalence of NAFLD has underlined the important public health implications of this disease. The pathogenesis of NAFLD involves the abnormal accumulation of free fatty acids, oxidative stress, endoplasmic reticulum (ER) stress, and a proinflammatory state in the liver. Schisandrin B (Sch B), an active dibenzooctadiene lignan isolated from the fruit of Schisandra chinensis (a traditional Chinese herb), was found to possess antihyperlipidemic, antioxidant, anti-ER stress, and anti-inflammatory activities in cultured hepatocytes in vitro and in rodent livers in vivo. Whereas a long-term, low dose regimen of Sch B induces an antihyperlipidemic response in obese mice fed a high fat diet, a single bolus high dose of Sch B increases serum/hepatic lipid levels in mice. This differential action of Sch B is likely related to a dose/time-dependent biphasic response on lipid metabolism in mice. The hepatoprotection afforded by Sch B against oxidative stress, ER stress, and inflammation has been widely reported. The ensemble of results suggests that Sch B may offer potential as a therapeutic agent for NAFLD. The optimal dose and duration of Sch B treatment need to be established in order to ensure maximal efficacy and safety when used in humans.

Schisandrin A (Sch A) and schisandrin B (Sch B) are active components of Schisandrae Fructus. We compared the biochemical mechanism underlying the anti-inflammatory action of Sch A and Sch B, using cultured lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and concanavalin (ConA)-stimulated mouse splenocytes. Pre-incubation with Sch A or Sch B produced an anti-inflammatory action in LPS-stimulated RAW264.7 cells, as evidenced by the inhibition of the pro-inflammatory c-Jun N-terminal kinases/p38 kinase/nuclear factor-kappa B signaling pathway as well as the suppression of various pro-inflammatory cytokines and effectors, with the extent of inhibition by Sch A being more pronounced. The greater activity of Sch A in anti-inflammatory response was associated with a greater decrease in cellular reduced glutathione (GSH) level and a greater increase in glutathione S-transferase activity than corresponding changes produced by Sch B. However, upon incubation, only Sch B resulted in the activation of the nuclear factor (erythroid-derived 2)-like factor 2 and the induction of a significant increase in the expression of thioredoxin (TRX) in RAW264.7 cells. The Sch B-induced increase in TRX expression was associated with the suppression of pro-inflammatory cytokines and effectors in LPS-stimulated macrophages. Studies in a mouse model of inflammation (carrageenan-induced paw edema) indicated that while long-term treatment with either Sch A or Sch B suppressed the extent of paw edema, only acute treatment with Sch A produced a significant degree of inhibition on the inflammatory response. Although only Sch A decreased the cellular GSH level and suppressed the release of pro-inflammatory cytokines and cell proliferation in ConA-simulated splenocytes in vitro, both Sch A and Sch B treatments, while not altering cellular GSH levels, suppressed ConA-stimulated splenocyte proliferation ex vivo. These results suggest that Sch A and Sch B may act differentially on activating GS

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver lesions ranging from hepatic steatosis, nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. The high global prevalence of NAFLD has underlined the important public health implications of this disease. The pathogenesis of NAFLD involves the abnormal accumulation of free fatty acids, oxidative stress, endoplasmic reticulum (ER) stress, and a proinflammatory state in the liver. Schisandrin B (Sch B), an active dibenzooctadiene lignan isolated from the fruit of Schisandra chinensis (a traditional Chinese herb), was found to possess antihyperlipidemic, antioxidant, anti-ER stress, and anti-inflammatory activities in cultured hepatocytes in vitro and in rodent livers in vivo. Whereas a long-term, low dose regimen of Sch B induces an antihyperlipidemic response in obese mice fed a high fat diet, a single bolus high dose of Sch B increases serum/hepatic lipid levels in mice. This differential action of Sch B is likely related to a dose/time-dependent biphasic response on lipid metabolism in mice. The hepatoprotection afforded by Sch B against oxidative stress, ER stress, and inflammation has been widely reported. The ensemble of results suggests that Sch B may offer potential as a therapeutic agent for NAFLD. The optimal dose and duration of Sch B treatment need to be established in order to ensure maximal efficacy and safety when used in humans.

Schisandrin A (Sch A) and schisandrin B (Sch B) are active components of Schisandrae Fructus. We compared the biochemical mechanism underlying the anti-inflammatory action of Sch A and Sch B, using cultured lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and concanavalin (ConA)-stimulated mouse splenocytes. Pre-incubation with Sch A or Sch B produced an anti-inflammatory action in LPS-stimulated RAW264.7 cells, as evidenced by the inhibition of the pro-inflammatory c-Jun N-terminal kinases/p38 kinase/nuclear factor-kappa B signaling pathway as well as the suppression of various pro-inflammatory cytokines and effectors, with the extent of inhibition by Sch A being more pronounced. The greater activity of Sch A in anti-inflammatory response was associated with a greater decrease in cellular reduced glutathione (GSH) level and a greater increase in glutathione S-transferase activity than corresponding changes produced by Sch B. However, upon incubation, only Sch B resulted in the activation of the nuclear factor (erythroid-derived 2)-like factor 2 and the induction of a significant increase in the expression of thioredoxin (TRX) in RAW264.7 cells. The Sch B-induced increase in TRX expression was associated with the suppression of pro-inflammatory cytokines and effectors in LPS-stimulated macrophages. Studies in a mouse model of inflammation (carrageenan-induced paw edema) indicated that while long-term treatment with either Sch A or Sch B suppressed the extent of paw edema, only acute treatment with Sch A produced a significant degree of inhibition on the inflammatory response. Although only Sch A decreased the cellular GSH level and suppressed the release of pro-inflammatory cytokines and cell proliferation in ConA-simulated splenocytes in vitro, both Sch A and Sch B treatments, while not altering cellular GSH levels, suppressed ConA-stimulated splenocyte proliferation ex vivo. These results suggest that Sch A and Sch B may act differentially on activating GS

Retinal degeneration is often progressive. This feature has provided a therapeutic window for intervention that may extend functional vision in patients. Even though this approach is feasible, few promising drug candidates are available. The scarcity of new drugs has motivated research to discover novel compounds through different sources. One such example is Schisandrin B (SchB), an active component isolated from the five-flavor fruit (Fructus Schisandrae) that is postulated in traditional Chinese medicines to exert prophylactic visual benefit. This SchB benefit was investigated in this study in pde6c(w59), a zebrafish retinal degeneration model. In this model, the pde6c gene (phosphodiesterase 6C, cGMP-specific, cone, alpha prime) carried a mutation which caused cone degeneration. This altered the local environment and caused the bystander rods to degenerate too. To test SchB on the pde6c(w59) mutants, a treatment concentration was first determined that would not cause morphological defects, and would initiate known physiological response. Then, the mutants were treated with the optimized SchB concentration before the appearance of retinal degeneration at 3 days postfertilization (dpf). The light sensation of animals was evaluated at 6 dpf by the visual motor response (VMR), a visual startle that could be initiated by drastic light onset and offset. The results show that the VMR of pde6c(w59) mutants towards light onset was enhanced by the SchB treatment, and that the initial phase of the enhancement was primarily mediated through the mutants' eyes. Further immunostaining analysis indicates that the treatment specifically reduced the size of the abnormally large rods. These observations implicate an interesting hypothesis: that the morphologically-improved rods drive the observed VMR enhancement. Together, these investigations have identified a possible visual benefit of SchB on retinal degeneration, a benefit that can potentially be further developed to extend fu

Nonalcoholic fatty liver disease (NAFLD) is a spectrum of liver lesions ranging from hepatic steatosis, nonalcoholic steatohepatitis, hepatic cirrhosis, and hepatocellular carcinoma. The high global prevalence of NAFLD has underlined the important public health implications of this disease. The pathogenesis of NAFLD involves the abnormal accumulation of free fatty acids, oxidative stress, endoplasmic reticulum (ER) stress, and a proinflammatory state in the liver. Schisandrin B (Sch B), an active dibenzooctadiene lignan isolated from the fruit of Schisandra chinensis (a traditional Chinese herb), was found to possess antihyperlipidemic, antioxidant, anti-ER stress, and anti-inflammatory activities in cultured hepatocytes in vitro and in rodent livers in vivo. Whereas a long-term, low dose regimen of Sch B induces an antihyperlipidemic response in obese mice fed a high fat diet, a single bolus high dose of Sch B increases serum/hepatic lipid levels in mice. This differential action of Sch B is likely related to a dose/time-dependent biphasic response on lipid metabolism in mice. The hepatoprotection afforded by Sch B against oxidative stress, ER stress, and inflammation has been widely reported. The ensemble of results suggests that Sch B may offer potential as a therapeutic agent for NAFLD. The optimal dose and duration of Sch B treatment need to be established in order to ensure maximal efficacy and safety when used in humans.

Previous studies have demonstrated that HCF1, a semipurified fraction of Cistanches Herba, causes weight reduction in normal diet- and high fat diet-fed mice. The weight reduction was associated with the induction of mitochondrial uncoupling and changes in metabolic enzyme activities in mouse skeletal muscle. To further investigate the biochemical mechanism underlying the HCF1-induced weight reduction, the effect of HCF1 and its active component, β-sitosterol (BSS), on C2C12 myotubes was examined. Incubation with HCF1/BSS caused a transient increase in mitochondrial membrane potential (MMP), possibly by fluidizing the mitochondrial inner membrane. The increase in MMP was paralleled to an increase in mitochondrial reactive oxygen species (ROS) production. Mitochondrial ROS, in turn, triggered a redox-sensitive induction of mitochondrial uncoupling by uncoupling protein 3 (UCP3). Biochemical analysis indicated that HCF1 was capable of activating an adenosine monophosphate-dependent protein kinase/peroxisome proliferator-activated receptor γ coactivator-1 pathway and thereby increased the expression of cytochrome c oxidase and UCP3. Animal studies using mitochondrial recoupler also confirmed the role of mitochondrial uncoupling in the HCF1-induced weight reduction. In conclusion, a HCF1/BSS causes the redox-sensitive induction of mitochondrial uncoupling and activation of AMPK/PGC-1 in C2C12 myotubes, with resultant reductions in body weight and adiposity by increased energy consumption.

This book provides a comprehensive but concise account of the commonly used herb in Chinese medicine, Schisandra chinensis (五味子). Of the six chapters covering botanical properties to product development, special emphasis is placed on recent pharmacological studies on active ingredients such as schisandrin B and schisandrin, as well as the integrative approach adopted in product development. Readers will be enlightened by the updates on pharmacological activities, underlying action mechanisms of Schisandra lignans and novel approach in product development featured in the book. Hence, this work will be a useful resource for researchers in both academia and industry.

Reactive oxygen species (ROS)-mediated activation of inflammasome is involved in the development of a wide spectrum of diseases. We aimed to investigate whether (−)schisandrin B [(−)Sch B], a phytochemical that can induce cellular antioxidant response, can suppress the inflammasome activation. Results showed that (−)Sch B can induce an nuclear factor erythroid 2-related factor 2-driven thioredoxin expression in primary peritoneal macrophages and cultured RAW264.7 macrophages. A 4-h priming of peritoneal macrophages with LPS followed by a 30-min incubation with ATP caused the activation of caspase 1 and the release of IL-1β, indicative of inflammasome activation. Although LPS/ATP did not activate inflammasome in RAW264.7 macrophages, it caused the ROS-dependent c-Jun N-terminal kinase1/2 (JNK1/2) activation and an associated lactate dehydrogenase (LDH) release in RAW264.7 macrophages, an indication of cytotoxicity. (−)Sch B suppressed the LPS/ATP-induced activation of caspase 1 and release of IL-1β in peritoneal macrophages. (−)Sch B also attenuated the LPS/ATP-induced ROS production, JNK1/2 activation and LDH release in RAW264.7 macrophages. The ability of (−)Sch B to suppress LPS/ATP-mediated inflammation in vitro was further confirmed by an animal study, in which schisandrin B treatment (2 mmol/kg p.o.) ameliorated the Imject Alum-induced peritonitis, as indicated by suppressions of caspase1 activation and plasma IL-1β level. The ensemble of results suggests that (−)Sch B may offer a promising prospect for preventing the inflammasome-mediated disorders.

Schisandrin B (Sch B) is one of the active dibenzocyclooctadiene lignans found in the Schisandrae Fructus. Experimental studies have shown that Sch B possesses various pharmacological properties, including anti-cancer, neuroprotective and nephroprotective activities. However, no detailed information on its biotransformation was reported in the literature. Here, we investigated the in vitro and in vivo metabolism of Sch B by using ultra-performance liquid chromatography coupled with tandem mass spectrometry. In vitro study detected and identified one oxygenated metabolite. Four metabolites were detected and identified from the in vivo study. The results indicated that the metabolism of Sch B mainly involved the demethylation of methoxy groups, the opening of five-member ring and the glucuronidation of metabolites in rats. The metabolites were identified for the first time by MS/MS analyses.

Doxorubicin (Dox) is a highly effective antineoplastic drug. However, Dox-induced apoptosis in cardiomyocytes leads to irreversible degenerative cardiomyopathy, which limits Dox clinical application. Schisandrin B (Sch B), a dibenzocyclooctadiene derivative isolated from the fruit of Schisandra chinensis, has been shown to protect against oxidative damage in liver, heart and brain tissues in rodents. In current study, we investigated possible protective effects of Sch B against Dox-induced cardiomyopathy in mice. Mice received a single injection of Dox (20 mg/kg IP). Five days after Dox administration, left ventricular (LV) performance was significantly depressed and was improved by Sch B treatment. Sch B prevented the Dox-induced increase in lipid peroxidation, nitrotyrosine formation, and metalloproteinase activation in the heart. In addition, the increased expression of phospho-p38 MAPK and phospho-MAPK activated mitogen kinase 2 levels by Dox were significantly suppressed by Sch B treatment. Sch B also attenuated Dox-induced higher expression of LV proinflammatory cytokines, cardiomyocyte DNA damage, myocardial apoptosis, caspase-3 positive cells and phopho-p53 levels in mice. Moreover, LV expression of NADPH oxidase subunits and reactive oxygen species were significantly less in Sch B treatment mice after Dox injection. These findings suggest that Sch B attenuates Dox-induced cardiotoxicity via antioxidative and anti-inflammatory effects.

Background: Currently, combined therapy using herbs and synthetic drugs has become a feasible therapeutic intervention against some diseases. The purpose of this study was to assess the effects of supplementation with fenofibrate (FF), a chemical drug used for the treatment of hyperlipidemia, and the aqueous extract of Schisandrae Fructus (SF, a Chinese herb) pulp (AqSF-P) or an SF-related synthetic analog, bicyclol (BY), on serum/hepatic lipid levels and liver status in normal and hypercholesterolemic (HCL) mice. Methods: Male mice obtained from the Institute of Cancer Research (ICR) were fed on a normal diet (ND) or high cholesterol/bile salt (0.5%/0.15%, w/w) diet (HCBD) containing FF (0.03% or 0.1%, w/w) with or without AqSF-P (0.3%-9.0%, based on crude herbal material, w/w) or BY (0.025%, w/w) for 10 days. Then serum lipid levels and alanine aminotransferase (ALT) activity, as well as hepatic triglyceride (TG), total cholesterol (TC), and glucose levels, were measured. Results: Oral supplementation with FF significantly reduced serum and hepatic TG, TC, and hepatic glucose levels (approximately 79%) in mice fed with ND or HCBD. FF supplementation combined with AqSF-P or BY increased FF-induced reduction in hepatic TC and TG contents in ND-fed mice (up to 67%) and in HCBD-fed mice (up to 54%), when compared with FF supplementation alone. Hepatic glucose-lowering effect of FF was enhanced (up to 19%) by AqSF-P cosupplementation in both normal and HCL mice. FF supplementation enhanced the excretion of fecal TC (by 75%) in mice fed with HCBD. Fecal TC contents were increased by 14%/9% in the combination therapy with FF and AqSF-P in ND-/HCBD-fed mice. Serum ALT activity was elevated by 45% in HCBD-fed mice. FF caused a significant increase in ALT activity by 198% and 120% in normal and HCL mice, respectively. BY markedly attenuated the ALT activity by 54% in mice fed with ND supplemented with 0.1% FF and by 42% in mice fed with HCBD supplemented with 0.03% FF. Conc

Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, is a ubiquitous compound widely distributed in many plants, fruits and medicinal herbs worldwide. A previous study in our laboratory has shown that UA can increase the mitochondrial ATP generation capacity (ATP-GC) and a glutathione-dependent antioxidant response, thereby protecting against oxidant injury in H9c2 cells in vitro and rat hearts ex vivo. However, the mechanism underlying the cellular protective effects induced by UA remains largely unknown. The present study has shown that pre-incubation with UA produces a transient increase in the mitochondrial membrane potential in H9c2 cells, which was accompanied by increases in mitochondrial reactive oxygen species (ROS) production. Studies using an antioxidant (dimethylthiourea) indicated that the suppression of mitochondrial ROS completely abrogated the UA-induced enhancement of mitochondrial uncoupling and glutathione reductase (GR)-mediated glutathione redox cycling, as well as protection against menadione cytotoxicity in H9c2 cells. Co-incubation with specific inhibitors of uncoupling proteins and GR almost completely prevented the cytoprotection afforded by UA against menadione-induced cytotoxicity in H9c2 cells. The results obtained so far suggest that UA-induced mitochondrial ROS production can elicit mitochondrial uncoupling and glutathione-dependent antioxidant responses, which offer cytoprotection against oxidant injury in H9c2 cells.

A topically used Chinese herbal paste, namely, CDNR, was designed to facilitate fracture healing which is usually not addressed in general hospital care. From our in vitro studies, CDNR significantly inhibited the release of nitric oxide from RAW264.7 cells by 51 to 77%. This indicated its anti-inflammatory effect. CDNR also promoted the growth of bone cells by stimulating the proliferation of UMR106 cells up to 18%. It also increased the biomechanical strength of the healing bone in a drill-hole defect rat model by 16.5% significantly. This result revealed its in vivo efficacy on facilitation of bone healing. Furthermore, the detection of the chemical markers of CDNR in the skin and muscle of the treatment area demonstrated its transdermal properties. However, CDNR did not affect the bone turnover markers in serum of the rats. With its anti-inflammatory and bone formation properties, CDNR is found effective in promoting bone healing.

According to traditional Chinese medicine (TCM) theory, Yang and Qi are driving forces of biological activities in the human body. Based on the crucial role of the mitochondrion in energy metabolism, we propose an extended view of Yang and Qi in the context of mitochondrion-driven cellular and body function. It is of interest that the clinical manifestations of Yang/Qi deficiencies in TCM resemble those of chronic fatigue syndrome in Western medicine, which is pathologically associated with mitochondrial dysfunction. By virtue of their ability to enhance mitochondrial function and its regulation, Yang- and Qi-invigorating tonic herbs, such as Cistanches Herba and Schisandrae Fructus, may therefore prove to be beneficial in the treatment of chronic fatigue syndrome with Yang deficiency.

Ursolic acid (UA), a natural pentacyclic triterpenoid carboxylic acid, is a ubiquitous compound widely distributed in many plants, fruits and medicinal herbs worldwide. A previous study in our laboratory has shown that UA can increase the mitochondrial ATP generation capacity (ATP-GC) and a glutathione-dependent antioxidant response, thereby protecting against oxidant injury in H9c2 cells in vitro and rat hearts ex vivo. However, the mechanism underlying the cellular protective effects induced by UA remains largely unknown. The present study has shown that pre-incubation with UA produces a transient increase in the mitochondrial membrane potential in H9c2 cells, which was accompanied by increases in mitochondrial reactive oxygen species (ROS) production. Studies using an antioxidant (dimethylthiourea) indicated that the suppression of mitochondrial ROS completely abrogated the UA-induced enhancement of mitochondrial uncoupling and glutathione reductase (GR)-mediated glutathione redox cycling, as well as protection against menadione cytotoxicity in H9c2 cells. Co-incubation with specific inhibitors of uncoupling proteins and GR almost completely prevented the cytoprotection afforded by UA against menadione-induced cytotoxicity in H9c2 cells. The results obtained so far suggest that UA-induced mitochondrial ROS production can elicit mitochondrial uncoupling and glutathione-dependent antioxidant responses, which offer cytoprotection against oxidant injury in H9c2 cells.