The American Journal of Chinese Medicine

Tai Chi Chuan (TCC), a traditional Chinese martial art, is well-documented to result in beneficial consequences in physical and mental health. TCC is regarded as a mind-body exercise that is comprised of physical exercise and meditation. Favorable effects of TCC on body balance, gait, bone mineral density, metabolic parameters, anxiety, depression, cognitive function, and sleep have been previously reported. However, the underlying mechanisms explaining the effects of TCC remain largely unclear. Recently, advances in neuroimaging technology have offered new investigative opportunities to reveal the effects of TCC on anatomical morphologies and neurological activities in different regions of the brain. These neuroimaging findings have provided new clues for revealing the mechanisms behind the observed effects of TCC. In this review paper, we discussed the possible effects of TCC-induced modulation of brain morphology, functional homogeneity and connectivity, regional activity and macro-scale network activity on health. Moreover, we identified possible links between the alterations in brain and beneficial effects of TCC, such as improved motor functions, pain perception, metabolic profile, cognitive functions, mental health and sleep quality. This paper aimed to stimulate further mechanistic neuroimaging studies in TCC and its effects on brain morphology, functional homogeneity and connectivity, regional activity and macro-scale network activity, which ultimately lead to a better understanding of the mechanisms responsible for the beneficial effects of TCC on human health.

Smilax glabra (SG) Roxb., a well-known traditional Chinese medicine, has been extensively used worldwide for its marked pharmacological activities for treating syphilitic poisoned sores, limb hypertonicity, morbid leucorrhea, eczema pruritus, strangury due to heat, carbuncle toxin, and many other human ailments. Approximately 200 chemical compounds have been isolated from SG Roxb., and the major components have been determined to be flavonoids and flavonoid glycosides, phenolic acids, and steroids. Among these active compounds, the effects of astilbin, which is used as a quality control marker to determine the quality of SG Roxb., have been widely investigated. Based on in vivo and in vitro studies, the primary active components of SG Roxb. possess various pharmacological activities, such as cytotoxic, anti-inflammatory and immune-modulatory effects, anti-oxidant, hepatoprotective, antiviral, antibacterial, and cardiovascular system protective activities. However, an extensive study to determine the relationship between the chemical compositions and pharmacological effects of SG Roxb. has not been conducted and is worth of our study. Improving the means of utilizing the effects of SG is crucial. The present paper reviews the ethnopharmacology, phytochemistry, and pharmacology of SG Roxb. and assesses its ethnopharmacological use in order to explore its therapeutic potential for future research.

Sanguisorba officinalis Linne (S. officinalis, Rosaceae) has been used as a medicinal plant for the treatment of burns, hematemesis, melena, intestinal infections, and dermatitis for a long time in China, Korea, and Japan. The therapeutic efficacy of this herb is intimately associated with its anti-oxidant, anti-inflammatory, antiviral, antifungal, hemostatic, and anticancer activities. Its root contains triterpenoid saponins (zigyuglycoside I: C${}_{41}$H${}_{66}$O${}_{13}$ and ziyuglycoside II: C${}_{35}$H${}_{56}$O₈) and tannins (sanguiin H-6: C${}_{82}$H${}_{54}$O${}_{52}$). It has been recently revealed that these active constituents of S. officinalis possess antiwrinkle properties without cytotoxicity. They also have anticancer effects by inducing apoptosis and cell cycle arrest. Moreover, they can inhibit proliferative tumorigenesis. The underlying mechanism involved in the pharmacological actions of these active constituents is mainly related to p38 MAPK signaling. Although various studies have reported its therapeutic activities and major chemical components, review articles that extensively organize various properties of S. officinalis and its major constituents are still scarce. Taken together, the objective of this paper is to provide overall pharmacological and phytochemical profiles of S. officinalis and its constituents (including ziyuglycoside I, ziyuglycoside II, and sanguiin H-6), and their potential roles in clinical applications for the treatment of inflammatory diseases, bleeding disorders, and cancer.

Flavonoid compound scutellarin (Scu) is quite frequently met in the plant kingdom, particularly in the genus Scutellaria (Lamiaceae) and Erigeron (Asteraceae). The extract of the herb of Erigeron breviscapus, containing this component in high amount, has been used for many years in traditional Chinese medicine. In recent years, studies have made great progress on the usefulness of Scu for treating various diseases by testing its mechanism of action. They support the traditional use of Scu rich plant in heart and cerebral ischemia. Scu can potentially be applied in Alzheimer’s disease, Helicobacter pylori infection, vascular complications of diabetes and as an inhibitor of certain carcinomas. Various methods were designed to improve its isolation from plant material, solubility, absorption and bioavailability. On the basis of recent studies, it is suggested that Scu could be a promising candidate for new natural drug and deserves particular attention in further research and development.

Yak is a wild bovine species living on the Qinghai Tibet Plateau that demonstrates good adaptability to the hypoxic environment. Chicoric acid, a natural phenolic compound, is known as having anti-oxidant, antiviral, anti-inflammatory and analgesic properties. However, its effect on hypoxia adaptability of yak is still unclear. In this study 40 yaks were selected that were of similar age, parity and weight, and divided into the control group and experimental groups 1, 2, 3, randomly. Results showed that chicoric acid significantly improved RBC, HGB, and WBC. There are significantly beneficial effects to increasing total protein contents ($P<0.05$): all treatments increased HDL-C contents, and supplementations 100mg/h significantly decreased the content of TG on the 60th day ($P<0.05$). Contents of the serum related enzymes like ALP, GOP and GPT showed varying degrees of change, but no significant differences and the indexes of anti-oxidant capacity (T-AOC and GSH-Px) were significantly improved ($P<0.05$), but MDA was decreased ($P<0.05$) under the action of the chicoric acid. Hypoxia-inducible factor in serum such as HIF-2$\alpha$, EPO, ROS, Fe${}^{3+}$ and Tf are all significantly decreased ($P<0.05$). The myocardial mitochondrial parameters mtDNA, UCP2, PGC1-$\alpha$, NRF1 and mitochondrial complexes were altered remarkably. Some indicators of glucose metabolism presented variation trends. Taken together, chicoric acid has shown a positive effect on the adaptive ability of yak in high altitude, hypoxic environment in plateau areas. Our findings reported a new potential means to enhance immunity and inflammatory response and improve the anti-oxidant capacity.

The fruit of Vaccinium bracteatum Thunb. (VBF) is commonly known as the oriental blueberry in Korea. The aim of this study was to evaluate the antidepressant-like effects of water VBF extract (VBFW) in a mouse model of chronic restraint stress (CRS) and to identify the underlying mechanisms of its action. The behavioral effects of VBFW were assessed in the forced swim test (FST) and open field test (OFT). The levels of serum corticosterone (CORT), brain monoamines, in addition to the extracellular signal-regulated kinases (ERKs)/protein kinase B (Akt) signaling pathway were evaluated. VBFW treatment significantly reduced the immobility time and increased swimming time in FST without altering the locomotor activity in unstressed mice. Furthermore, CRS mice treated with VBFW exhibited a significantly decreased immobility time in FST and serum CORT, increased locomotor activity in OFT, and enhanced brain monoamine neurotransmitters. Similarly, VBFW significantly upregulated the ERKs/Akt signaling pathway in the hippocampus and PFC. In addition, VBFW may reverse CORT-induced cell death by enhancing cyclic AMP-responsive element-binding protein expression through the up-regulation of ERKs/Akt signaling pathways. In addition, VBFW showed the strong antagonistic effect of the 5-HT${}_{2\mathrm{\text{A}}}$ receptor by inhibiting 5-HT-induced intracellular Ca${}^{2+}$ and ERK1/2 phosphorylation. Our study provides evidence that antidepressant-like effects of VBFW might be mediated by the regulation of monoaminergic systems and glucocorticoids, which is possibly associated with neuroprotective effects and antagonism of 5-HT${}_{2\mathrm{\text{A}}}$ receptor.

Alzheimer’s disease (AD) is the most common neurodegenerative disease in the world. Although the exact causes of AD have not yet been fully elucidated, cholinergic dysfunction, mitochondrial damage, oxidative stress and neuroinflammation have been recognized as influential factors. Current drugs that are designed to address only a single target are unable to mitigate or prevent the progression of this complicated disease, so new disease-modifying drugs are urgently needed. Chinese herbs with thousand years of effective usage might be a good source for potential drugs. Gardenia jasminoides J. Ellis (Fructus Gardenia) is a common traditional Chinese medicine with tranquilizing effects, which is an important component of widely-used traditional Chinese medicine for dementia. GJ-4 is crocin richments extracted from Gardenia jasminoides J. Ellis. In our study, we attempted to observe the effects of GJ-4 on learning and memory injury induced by amyloid-$\beta$ 25-35 (A${\beta }_{25-35})$ injection in mice. Treatment with GJ-4 dose-dependently enhanced the memory and cognition ability of A${\beta }_{25-35}$-injected mice. Preliminary mechanistic studies revealed the protective effect of GJ-4 was related to its protection of neurons and cholinergic dysfunction. The mechanistic results also indicated that GJ-4 could enhance antioxidant capacity and attenuate neuroinflammation. Our results implied that GJ-4 might be a promising drug to improve cognitive and memory impairment, with multiple targets.

$p$-coumaric acid ($p$-CA) is a common compound found in medicinal herbs, including Bambusae Caulis in Taeniam (BC). It has been used to treat various diseases in China and Korea. Our previous study demonstrated that BC inhibits pulmonary and intestinal inflammation. In the present study, we used cigarette smoke (CS) to induce lung inflammation in vivo, and investigated the anti-inflammatory effects of $p$-CA on CS-induced inflammatory mice model. Mice were treated with BC and $p$-CA via oral injection 2h before CS exposure. The body weight and the inflammatory cells in the bronchoalveolar lavage fluid were measured. The levels of relative inflammatory factors were confirmed by enzyme-linked immunosorbent assay. The lung histological changes were examined by hematoxylin and eosin staining. Also, the protein level of nuclear factor-$\kappa$B (NF-$\kappa$B) was evaluated by Western blotting. Our results indicated that BC and $p$-CA inhibited CS-induced lung inflammation by regulating pro-inflammatory productions such as cytokines, chemokine, protease and NF-$\kappa$B. Consequently, these data demonstrated that $p$-CA inhibited pulmonary inflammation by suppressing NF-$\kappa$B activity, through which pro-inflammatory mediators were regulated. Therefore, $p$-CA, which was shown to be a major component of BC, can be considered as a strong therapeutic candidate for treating pulmonary inflammatory diseases.

Eucalyptus globulus Labill. (E. globulus, Myrtaceae) is used in Europe as a traditional folk remedy for inflammation-related disorders such as arthritis, diabetes, asthma, and gout. We investigated this study to evaluate the protective effects of E. globulus extract (EG) on inflammatory responses, and provide scientific and mechanistic evidence in in vitro and in vivo experimental models. LPS-stimulated murine bone marrow-derived macrophages (BMDMs) were used to study the regulatory effect of EG on inflammasome activation in vitro. Monosodium urate (MSU)-induced peritonitis was used to study the effect of EG in an in vivo murine model. EG suppressed IL-$1\beta$ secretion via the regulation of apoptosis-associated speck-like proteins containing a CARD (ASC) oligomerization and caspase-1 maturation, leading to the inhibition of inflammasome activation. In the in vivo study, EG suppressed the MSU-induced peritonitis by attenuating interleukin (IL)-1$\beta$, providing scientific support for its traditional use in the treatment of inflammation-related disorders.

Momordica charantia known as bitter melon is a representative medicinal plant reported to exhibit numerous pharmacological activities such as antibacterial, antidiabetic, anti-inflammatory, anti-oxidant, antitumor, and hypoglycemic actions. Although this plant has high ethnopharmacological value for treating inflammatory diseases, the molecular mechanisms by which it inhibits the inflammatory response are not fully understood. In this study, we aim to identify the anti-inflammatory mechanism of this plant. To this end, we studied the effects of its methanol extract (Mc-ME) on lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages. Specifically, we evaluated nitric oxide (NO) production, mRNA expression of inflammatory genes, luciferase reporter gene activity, and putative molecular targets. Mc-ME blocked NO production in a dose-dependent manner in RAW264.7 cells; importantly, no cytotoxicity was observed. Moreover, the mRNA expression levels of inducible NO synthase (iNOS) and cyclooxygenase (COX)-2 were decreased by Mc-ME treatment in a dose-dependent manner. Luciferase assays and nuclear lysate immunoblotting analyses strongly indicated that Mc-ME decreases the levels of p65 [a nuclear factor (NF)-$\kappa$B subunit] and c-Fos [an activator protein (AP)-1 subunit]. Whole lysate immunoblotting assays, luciferase assays, and overexpression experiments suggested that transforming growth factor $\beta$-activated kinase 1 (TAK1) is targeted by Mc-ME, thereby suppressing NF-$\kappa$B and AP-1 activity via downregulation of extracellular signal-regulated kinases (ERKs) and AKT. These results strongly suggest that Mc-ME exerts its anti-inflammatory activity by reducing the action of TAK1, which also affects the activation of NF-$\kappa$B and AP-1.

Dendropanax morbifera Leveille (Araliaceae) is an endemic species that grows in Southwestern Korea and has been used as a folk medicine. Several studies reported that D. morbifera leaves have diverse therapeutic potentials. We found that the water extract of D. morbifera leaves increased the growth of EL-4 T cells. The water extract was divided into five fractions: $n$-hexane, chloroform, ethyl acetate, $n$-butanol, and water layers. The ethyl acetate (W-EA) fraction showed a more significant effect than the other fractions on the growth of EL-4 T cells, splenocytes, and isolated murine CD4${}^{+}$ T cells. We evaluated the W-EA fraction for its immunomodulatory effects focusing on T cell functions. First, we tested the effect of the W-EA fraction on the regulation of interleukin-2 (IL-2), a potent T cell growth factor. The W-EA fraction significantly increased IL-2 secretion in EL-4 T cells activated with phorbol 12-myristate 13-acetate (PMA) and ionomycin (Io). In addition, the W-EA fraction increased interferon-gamma (IFN-$\gamma )$ production in isolated murine splenocytes activated with Concanavalin A (ConA). Next, we examined the effect of the W-EA fraction on the regulation of transcriptional factors related to IL-2 production in T cells. The W-EA fraction significantly increased PMA/Io-induced promoter activity of a nuclear factor of activated T cells (NF-AT) in EL-4 T cells, but did not show any significant effects on the promoters of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-$\kappa$B). These results indicate that the W-EA fraction from water extract of D. morbifera leaves enhances IL-2 production at the transcriptional levels via the up-regulation of NF-AT in PMA/Io-activated EL-4 T cells.

Oxidative stress induced by reactive oxygen species is the main cause of various liver diseases. This study investigated the hepatoprotective effect of Epimedium koreanum Nakai water extract (EKE) against arachidonic acid (AA)$+$iron-mediated cytotoxicity in HepG2 cells and carbon tetrachloride (CCl₄-)-mediated acute liver injury in mice. Pretreatment with EKE (30 and 100$\mu$g/mL) significantly inhibited AA$+$iron-mediated cytotoxicity in HepG2 cells by preventing changes in the expression of cleaved caspase-3 and poly(ADP-ribose) polymerase. EKE attenuated hydrogen peroxide production, glutathione depletion, and mitochondrial membrane dysfunction. EKE also increased the nuclear translocation of nuclear factor erythroid 2-related factor 2 (Nrf2), transactivated anti-oxidant response element harboring luciferase activity, and induced the expression of anti-oxidant genes. Furthermore, the cytoprotective effect of EKE against AA$+$iron was blocked in Nrf2 knockout cells. Ultra-performance liquid chromatography analysis showed that EKE contained icariin, icaritin, and quercetin; icaritin and quercetin were both found to protect HepG2 cells from AA$+$iron via Nrf2 activation. In a CCl₄-induced mouse model of liver injury, pretreatment with EKE (300mg/kg) for four consecutive days ameliorated CCl₄-mediated increases in serum aspartate aminotransferase activity, histological activity index, hepatic parenchyma degeneration, and inflammatory cell infiltration. EKE also decreased the number of nitrotyrosine-, 4-hydroxynonenal-, cleaved caspase-3-, and cleaved poly(ADP-ribose) polymerase-positive cells in hepatic tissues. These results suggest EKE is a promising candidate for the prevention or treatment of oxidative stress-related liver diseases via Nrf2 activation.