: Cerebral ischemic stroke is a disease with high prevalence and incidence. Its management focuse... more : Cerebral ischemic stroke is a disease with high prevalence and incidence. Its management focuses on rapid reperfusion with intravenous thrombolysis and endovascular thrombectomy. Both therapeutic strategies reduce disability, but the therapy time window is short, and the risk of bleeding is high. Natural products (NPs) have played a key role in drug discovery, especially for cancer and infectious diseases. However, they have made little progress in clinical translation and pose challenges to the treatment of stroke. Recently, with the investigation of precise mechanisms in cerebral ischemic stroke and the technological development of NP-based drug discovery, NPs are addressing these challenges and opening up new opportunities in cerebral stroke. Thus, in this review, we first summarize the structure and function of diverse NPs, including flavonoids, phenols, terpenes, lactones, quinones, alkaloids, and glycosides. Then we propose the comprehensive neuroprotective mechanism of NPs in cerebral ischemic stroke, which involves complex cascade processes of oxidative stress, mitochondrial damage, apoptosis or ferroptosis-related cell death, inflammatory response, and disruption of the blood-brain barrier (BBB). Overall, we stress the neuroprotective effect of NPs and their mechanism on cerebral ischemic stroke for a better understanding of the advances and perspective in NPs application that may provide a rationale for the development of innovative therapeutic regimens in ischemic stroke.
Astragalosides have been shown to enhance endurance exercise capacity in vivo and promote muscula... more Astragalosides have been shown to enhance endurance exercise capacity in vivo and promote muscular hypertrophy in vitro. However, it remains unknown whether astragalosides supplementation can alter inflammatory response and enhance muscle recovery after damage in humans. We therefore aimed to evaluate the effect of astragalosides supplementation on muscle’s intrinsic capacity to regenerate and repair itself after exercise-induced damage. Using a randomized double-blind placebo-controlled cross-over design, eleven male participants underwent 7 days of astragalosides supplementation (in total containing 4 mg of astragalosides per day) or a placebo control, following an eccentric exercise protocol. Serum blood samples and variables related to muscle function were collected prior to and immediately following the muscle damage protocol and also at 2 h, and 1, 2, 3, 5, and 7 days of the recovery period, to assess the pro-inflammatory cytokine response, the secretion of muscle regenerative...
Glioblastoma (GBM) is an aggressive brain tumor which is currently treated with temozolomide (TMZ... more Glioblastoma (GBM) is an aggressive brain tumor which is currently treated with temozolomide (TMZ). Tumors usually become resistant to TMZ and recur; no effective therapy is then available. Monoamine Oxidase A (MAO A) oxidizes monoamine neurotransmitters resulting in reactive oxygen species which cause cancer. This study shows that MAO A expression is increased in human glioma tissues and cell lines. MAO A inhibitors, clorgyline or the near-infrared-dye MHI-148 conjugated to clorgyline (NMI), were cytotoxic for glioma and decreased invasion in vitro. Using the intracranial TMZ-resistant glioma model, clorgyline or NMI alone or in combination with low-dose TMZ reduced tumor growth and increased animal survival. NMI was localized specifically to the tumor. Immunocytochemistry studies showed that the MAO A inhibitor reduced proliferation, microvessel density and invasion, and increased macrophage infiltration. In conclusion, we have identified MAO A inhibitors as potential novel stand-...
In our previous study, we found that Astragalus membranaceus extract (AM) promoted hypertrophy in... more In our previous study, we found that Astragalus membranaceus extract (AM) promoted hypertrophy in cultured skeletal myotubes through activating the PI3K/Akt/mTOR pathway as IGF‐1. PURPOSE: To investigate the effect of AM supplement following experimentally induced muscle damage by eccentric exercise on IGF‐1 level and muscle oxygenation. METHODS: In a randomized, cross‐over design, nine healthy male volunteers were subjected to exercise‐induced muscle damage. The effects of AM or placebo (PL) supplement on blood IL‐6 and IGF‐1 concentrations, muscle oxygenation (temporal changes of HHb, HbO2 concentrations, and TSI percentage), self‐reported delayed‐onset muscle soreness (by VAS score), and muscle strength (1RM) of leg extension were determined. Blood samples were taken before, immediately after exercise, and at 2 hr, 1, 2, 3 and 7 days post exercise. RESULTS: IL‐6 concentrations at 2 hr, and 2, 3, and 7 day after eccentric exercise of leg extension in the AM treatment (0.56 ± 0.07,...
PURPOSE:Herbal medicine has long been used in ergogenic aids for athletes but there is little sci... more PURPOSE:Herbal medicine has long been used in ergogenic aids for athletes but there is little scientific evidence for their actions. To investigate whether Angelica sinensis increases hypertrophy of myotubes through activating the PI3K/Akt/mTOR pathway, have been proposed to promote skeletal muscle hypertrophy and prevent muscle atrophy. METHODS:We examined the PI3K/Akt/mTOR pathway in C2C12 myotubes, a well-established in vitro model of skeletal muscle hypertrophy, with or without Angelica sinensis extract for 72 hours. RESULTS:In Angelica sinensis extract treated, the average myotube diameter was 1.34±0.13 fold to normal, which is significantly larger than the diameter in non-herbal supplements cultures. This indicates clearly that myotubes were hypertrophied by Angelica sinensis extract. Hypertrophy was largely suppressed by wortmannin or rapamycin, inhibitors of PI3K or mTOR, respectively. The PI3K inhibitor, wortmannin, decreased the diameter of Angelica sinensis extract treate...
The purpose of this study was to investigate the effects of a proprietary blend of soybean peptid... more The purpose of this study was to investigate the effects of a proprietary blend of soybean peptides, taurine, Pueraria isoflavone, and ginseng saponin complex (STPG capsule) on exercise performance in humans. Fourteen male volunteers were randomly assigned to two crossover treatments in which they consumed either four STPG capsules (STPG treatment) or placebo (P treatment) for 15 days before a 75% maximal oxygen uptake (VO(2max)) exhaustive cycling test. Blood samples and respiratory gas were collected prior to the exercise (Pre-Ex), at 10 (Ex-10), 15 (Ex-15), 20 (Ex-20), and 25 (Ex-25) minutes during exercise, and immediately after exercise (exhaustion) to assess the blood metabolites, cardiorespiratory responses, and energy substrate utilization. The result showed that exercise time to exhaustion of the 75% (VO(2max)) exhaustive cycling test of the STPG-treated subjects was significantly greater than with the P treatment (30.99 ± 2.01 vs. 28.05 ± 1.48 minutes). The plasma lactate concentrations at Ex-20 and Ex-25 in the STPG treatment were significantly lower with STPG treatment than with P treatment (10.5 ± 0.7 vs. 11.5 ± 0.8 and 10.7 ± 0.9 vs.12.3 ± 1.0 mmol/L, respectively). Nonesterified fatty acid levels at Ex-15, Ex-20, Ex-25, and exhaustion in the STPG group (0.27 ± 0.03, 0.32 ± 0.04, 0.32 ± 0.06, and 0.37 ± 0.05 mmol/L, respectively) were significantly higher than those in the P treatment (0.21 ± 0.03, 0.23 ± 0.03, 0.24 ± 0.03, and 0.25 ± 0.03 mmol/L, respectively). It was concluded that supplementation of four capsules (2 g) of STPG complex, consisting of soybean peptides, taurine, Pueraria isoflavone, and ginseng saponin, for 15 days was effective in promoting utilization of free fatty acids and improving exhaustive cycling test performance in humans.
The aim of this study was to evaluate the effects of purple sweet potato leaves (PSPL) consumptio... more The aim of this study was to evaluate the effects of purple sweet potato leaves (PSPL) consumption on oxidative stress markers in a healthy, nontrained, young male population after completing a running exercise protocol. A crossover design was applied, with 15 subjects participating in a two-step dietary intervention period. Each subject was given a high- (PSPL group) or low-polyphenol (control group) diet for 7 days with a 14-day washout period. After each dietary intervention period, all subjects performed 1 h of treadmill running at a speed corresponding to 70% of each subject's individual maximal oxygen uptake (V̇o2max). Blood samples were taken before exercise and at 0, 1, and 3 h after exercise. Compared with the control group, PSPL consumption significantly increased plasma total polyphenols concentration and total antioxidant power (i.e., the ferric-reducing ability of plasma) in the PSPL group. The markers of oxidative damage, plasma TBARS and protein carbonyl, signific...
Astragalus membranaceus (AM) is classified as a high-class traditional herbal medicine, which has... more Astragalus membranaceus (AM) is classified as a high-class traditional herbal medicine, which has strengthened vitality and multifunctional pharmacological activities, but limited empirical evidence is available to support its effects in muscular hypertrophy. It evokes skeletal muscle hypertrophy by increasing anabolic pathway, which is essential to prevent sarcopenia in elderly population. In this study, we examined the effects of AM on skeletal muscle hypertrophy by focusing on the molecular mechanism. We employed an in vitro model to investigate whether AM-treated skeletal muscle, as represented by myotube C2C12 cells, was hypertrophic, and to further investigate the efficacy of AM-activated phosphorylation of PI3K/Akt/mTOR signaling that must occur prior to myotube hypertrophy. The results showed that the myotubes formed larger multinucleated myotubes with increased diameter and thickness (1.16-fold relative to control group, p < 0.05). Administration of PI3K and mTOR inhibit...
: Cerebral ischemic stroke is a disease with high prevalence and incidence. Its management focuse... more : Cerebral ischemic stroke is a disease with high prevalence and incidence. Its management focuses on rapid reperfusion with intravenous thrombolysis and endovascular thrombectomy. Both therapeutic strategies reduce disability, but the therapy time window is short, and the risk of bleeding is high. Natural products (NPs) have played a key role in drug discovery, especially for cancer and infectious diseases. However, they have made little progress in clinical translation and pose challenges to the treatment of stroke. Recently, with the investigation of precise mechanisms in cerebral ischemic stroke and the technological development of NP-based drug discovery, NPs are addressing these challenges and opening up new opportunities in cerebral stroke. Thus, in this review, we first summarize the structure and function of diverse NPs, including flavonoids, phenols, terpenes, lactones, quinones, alkaloids, and glycosides. Then we propose the comprehensive neuroprotective mechanism of NPs in cerebral ischemic stroke, which involves complex cascade processes of oxidative stress, mitochondrial damage, apoptosis or ferroptosis-related cell death, inflammatory response, and disruption of the blood-brain barrier (BBB). Overall, we stress the neuroprotective effect of NPs and their mechanism on cerebral ischemic stroke for a better understanding of the advances and perspective in NPs application that may provide a rationale for the development of innovative therapeutic regimens in ischemic stroke.
Astragalosides have been shown to enhance endurance exercise capacity in vivo and promote muscula... more Astragalosides have been shown to enhance endurance exercise capacity in vivo and promote muscular hypertrophy in vitro. However, it remains unknown whether astragalosides supplementation can alter inflammatory response and enhance muscle recovery after damage in humans. We therefore aimed to evaluate the effect of astragalosides supplementation on muscle’s intrinsic capacity to regenerate and repair itself after exercise-induced damage. Using a randomized double-blind placebo-controlled cross-over design, eleven male participants underwent 7 days of astragalosides supplementation (in total containing 4 mg of astragalosides per day) or a placebo control, following an eccentric exercise protocol. Serum blood samples and variables related to muscle function were collected prior to and immediately following the muscle damage protocol and also at 2 h, and 1, 2, 3, 5, and 7 days of the recovery period, to assess the pro-inflammatory cytokine response, the secretion of muscle regenerative...
Glioblastoma (GBM) is an aggressive brain tumor which is currently treated with temozolomide (TMZ... more Glioblastoma (GBM) is an aggressive brain tumor which is currently treated with temozolomide (TMZ). Tumors usually become resistant to TMZ and recur; no effective therapy is then available. Monoamine Oxidase A (MAO A) oxidizes monoamine neurotransmitters resulting in reactive oxygen species which cause cancer. This study shows that MAO A expression is increased in human glioma tissues and cell lines. MAO A inhibitors, clorgyline or the near-infrared-dye MHI-148 conjugated to clorgyline (NMI), were cytotoxic for glioma and decreased invasion in vitro. Using the intracranial TMZ-resistant glioma model, clorgyline or NMI alone or in combination with low-dose TMZ reduced tumor growth and increased animal survival. NMI was localized specifically to the tumor. Immunocytochemistry studies showed that the MAO A inhibitor reduced proliferation, microvessel density and invasion, and increased macrophage infiltration. In conclusion, we have identified MAO A inhibitors as potential novel stand-...
In our previous study, we found that Astragalus membranaceus extract (AM) promoted hypertrophy in... more In our previous study, we found that Astragalus membranaceus extract (AM) promoted hypertrophy in cultured skeletal myotubes through activating the PI3K/Akt/mTOR pathway as IGF‐1. PURPOSE: To investigate the effect of AM supplement following experimentally induced muscle damage by eccentric exercise on IGF‐1 level and muscle oxygenation. METHODS: In a randomized, cross‐over design, nine healthy male volunteers were subjected to exercise‐induced muscle damage. The effects of AM or placebo (PL) supplement on blood IL‐6 and IGF‐1 concentrations, muscle oxygenation (temporal changes of HHb, HbO2 concentrations, and TSI percentage), self‐reported delayed‐onset muscle soreness (by VAS score), and muscle strength (1RM) of leg extension were determined. Blood samples were taken before, immediately after exercise, and at 2 hr, 1, 2, 3 and 7 days post exercise. RESULTS: IL‐6 concentrations at 2 hr, and 2, 3, and 7 day after eccentric exercise of leg extension in the AM treatment (0.56 ± 0.07,...
PURPOSE:Herbal medicine has long been used in ergogenic aids for athletes but there is little sci... more PURPOSE:Herbal medicine has long been used in ergogenic aids for athletes but there is little scientific evidence for their actions. To investigate whether Angelica sinensis increases hypertrophy of myotubes through activating the PI3K/Akt/mTOR pathway, have been proposed to promote skeletal muscle hypertrophy and prevent muscle atrophy. METHODS:We examined the PI3K/Akt/mTOR pathway in C2C12 myotubes, a well-established in vitro model of skeletal muscle hypertrophy, with or without Angelica sinensis extract for 72 hours. RESULTS:In Angelica sinensis extract treated, the average myotube diameter was 1.34±0.13 fold to normal, which is significantly larger than the diameter in non-herbal supplements cultures. This indicates clearly that myotubes were hypertrophied by Angelica sinensis extract. Hypertrophy was largely suppressed by wortmannin or rapamycin, inhibitors of PI3K or mTOR, respectively. The PI3K inhibitor, wortmannin, decreased the diameter of Angelica sinensis extract treate...
The purpose of this study was to investigate the effects of a proprietary blend of soybean peptid... more The purpose of this study was to investigate the effects of a proprietary blend of soybean peptides, taurine, Pueraria isoflavone, and ginseng saponin complex (STPG capsule) on exercise performance in humans. Fourteen male volunteers were randomly assigned to two crossover treatments in which they consumed either four STPG capsules (STPG treatment) or placebo (P treatment) for 15 days before a 75% maximal oxygen uptake (VO(2max)) exhaustive cycling test. Blood samples and respiratory gas were collected prior to the exercise (Pre-Ex), at 10 (Ex-10), 15 (Ex-15), 20 (Ex-20), and 25 (Ex-25) minutes during exercise, and immediately after exercise (exhaustion) to assess the blood metabolites, cardiorespiratory responses, and energy substrate utilization. The result showed that exercise time to exhaustion of the 75% (VO(2max)) exhaustive cycling test of the STPG-treated subjects was significantly greater than with the P treatment (30.99 ± 2.01 vs. 28.05 ± 1.48 minutes). The plasma lactate concentrations at Ex-20 and Ex-25 in the STPG treatment were significantly lower with STPG treatment than with P treatment (10.5 ± 0.7 vs. 11.5 ± 0.8 and 10.7 ± 0.9 vs.12.3 ± 1.0 mmol/L, respectively). Nonesterified fatty acid levels at Ex-15, Ex-20, Ex-25, and exhaustion in the STPG group (0.27 ± 0.03, 0.32 ± 0.04, 0.32 ± 0.06, and 0.37 ± 0.05 mmol/L, respectively) were significantly higher than those in the P treatment (0.21 ± 0.03, 0.23 ± 0.03, 0.24 ± 0.03, and 0.25 ± 0.03 mmol/L, respectively). It was concluded that supplementation of four capsules (2 g) of STPG complex, consisting of soybean peptides, taurine, Pueraria isoflavone, and ginseng saponin, for 15 days was effective in promoting utilization of free fatty acids and improving exhaustive cycling test performance in humans.
The aim of this study was to evaluate the effects of purple sweet potato leaves (PSPL) consumptio... more The aim of this study was to evaluate the effects of purple sweet potato leaves (PSPL) consumption on oxidative stress markers in a healthy, nontrained, young male population after completing a running exercise protocol. A crossover design was applied, with 15 subjects participating in a two-step dietary intervention period. Each subject was given a high- (PSPL group) or low-polyphenol (control group) diet for 7 days with a 14-day washout period. After each dietary intervention period, all subjects performed 1 h of treadmill running at a speed corresponding to 70% of each subject's individual maximal oxygen uptake (V̇o2max). Blood samples were taken before exercise and at 0, 1, and 3 h after exercise. Compared with the control group, PSPL consumption significantly increased plasma total polyphenols concentration and total antioxidant power (i.e., the ferric-reducing ability of plasma) in the PSPL group. The markers of oxidative damage, plasma TBARS and protein carbonyl, signific...
Astragalus membranaceus (AM) is classified as a high-class traditional herbal medicine, which has... more Astragalus membranaceus (AM) is classified as a high-class traditional herbal medicine, which has strengthened vitality and multifunctional pharmacological activities, but limited empirical evidence is available to support its effects in muscular hypertrophy. It evokes skeletal muscle hypertrophy by increasing anabolic pathway, which is essential to prevent sarcopenia in elderly population. In this study, we examined the effects of AM on skeletal muscle hypertrophy by focusing on the molecular mechanism. We employed an in vitro model to investigate whether AM-treated skeletal muscle, as represented by myotube C2C12 cells, was hypertrophic, and to further investigate the efficacy of AM-activated phosphorylation of PI3K/Akt/mTOR signaling that must occur prior to myotube hypertrophy. The results showed that the myotubes formed larger multinucleated myotubes with increased diameter and thickness (1.16-fold relative to control group, p < 0.05). Administration of PI3K and mTOR inhibit...
Uploads
Papers by Tzu-Shao Yeh