Effect and mechanism of acupuncture on endogenous and exogenous stem cells in disease treatment: A therapeutic review.

Acupuncture is effective intervention, particularly in nerve, endocrine diseases and immune diseases. The potential mechanisms mediating the effects of acupuncture include anti-inflammatory and oxidative stress, inhibition of cell apoptosis, and stimulation of the proliferation and differentiation of endogenous stem cells. Traditional Chinese medicine combined with stem cell transplantation have a synergistic effect in the treatment of diseases. Increasing studies have found that acupuncture can promote the proliferation, differentiation, homing and survival of exogenous stem cells. This article reviews the mechanism of acupuncture and Chinese herbs on endogenous stem cells and exogenous stem cells in the combined intervention of diverse disorders and the major problems in past 15 years, which will provide a reference for future clinical research.

Electroacupuncture activates angiogenesis by regulating the PI3K/Pten/Thbs1 signaling pathway to promote the browning of adipose tissue in HFD-induced obese mice.

This study investigated the effect of electroacupuncture (EA) on the browning of white adipose tissue (WAT) via angiogenesis and its potential mechanism in obese mice. Four-week-old male C56BL/6 mice were randomly divided into a high-fat diet (HFD) and a normal chow diet (ND) group. After 12 weeks, HFD mice were randomly divided into two groups to receive or not receive EA for 3 weeks. After EA treatment, body weight, adipocyte size, serum glucose (GLU), triacylglycerol (TG), cholesterol (CHO), leptin (Lep), monocyte chemoattractant protein-1 (MCP-1), WAT browning-related genes, angiogenesis-related genes, and the PI3K/Pten/Thbs1 signaling pathway were evaluated. The results indicated that EA significantly reduced body weight, adipocyte size, and serum concentrations of GLU, TG, CHO, Lep and MCP-1 and promoted WAT browning. Angiogenesis and the PI3K/Pten/Thbs1 signaling pathway were all activated by EA intervention. The expression levels were consistent with the results of RNA-seq and confirmed via qRTPCR and WB. Our study showed that EA may activate angiogenesis via the PI3K/Pten/Thbs1 signaling pathway in WAT, thereby promoting the browning and thermogenesis of adipose tissue.

The potential of Chinese medicines in the treatment of hyperuricemia.

The annual incidence of gout is increasing along with lifestyle and dietary changes. Accumulation of urate crystals in joints and tissues when the amount of uric acid exceeds its saturation concentration causes acute inflammation that leads to gout. Reducing the serum uric acid concentration is the key to treating gout. Allopurinol, febuxostat, benzbromarone, and other drugs are effective, but side effects of treatment such as toxicity and recurrence after drug withdrawal cannot be ignored. Recent studies have found that many Chinese medicines are effective and safe, provide durable efficacy, and are associated with low recurrence rates. This article reviews recent investigations of Chinese medicines for lowering uric acid, including components such as berberine, luteolin, and others; single medicines such as Smilax glabra Roxb., Reynoutria japonica Houtt., and Plantago asiatica L.; and compounds such as Wuling Powder and Compound Tufuling Granules. Mechanisms of lowering uric acid, including inhibiting uric acid production and promoting uric acid excretion are discussed. Clinical studies and basic research are reviewed.

Icariin and its metabolites regulate lipid metabolism: From effects to molecular mechanisms.

Icariin has a variety of biological activities, such as lipid-lowering effects, and has attracted widespread attention in recent years. However, it is not clear whether lipid-lowering effect is that multiple metabolites or a particular component plays a major role. It is known that icariin has a variety of metabolites in the body, including icariside I, icariside II, icaritin, desmethylicaritin, and other metabolites. Many of these studies have shown that the metabolites of icariin have a lipid-lowering effect. This paper focuses on the lipid-regulating effects of icariin and its metabolites in vitro and in vivo, and highlights the mechanisms involved. Icariin may have potential in the development of therapeutic strategies to regulate lipid metabolism.

Music-based interventions to improve fibromyalgia syndrome: A meta-analysis.

OBJECTIVE: We evaluated the effects of music therapy on pain, depression and quality of life in patients with fibromyalgia. METHODS: Ten online databases were searched to identify randomized controlled trials that investigated the effects of music therapy on fibromyalgia patients, published up to 1st January 2019. The results were filtered and independently extracted. Statistical heterogeneity was assessed using the chi-square test. According to the outcome of the heterogeneity indices, either a fixed effect or a random effect model was used. RESULTS: In total, seven randomized controlled trials were included. The Pain Visual Analog Scale, the McGill Pain Scale, the Beck Depression Scale and the Fibromyalgia Impact Questionnaire were used as outcome measures. Our evidence indicated that patient intervention with music therapy had lower scores on the Pain Visual Analog Scale (95% confidence interval [CI] -2.22 to -1.18, Z = 6.44, P < 0.00001, four studies) and Beck Depression Scale (95% CI -0.65 to -0.03, Z = 2.17, P = 0.03, two studies). No significant differences were observed on the McGill Pain Scale between the music intervention and control groups (95% CI -0.83 to -0.09, Z = 1.59, P = 0.11). A general qualitative description of the Fibromyalgia Impact Questionnaire results was given due to high heterogeneity (I2 = 96%, P < 0.00001). CONCLUSIONS: The music therapy is superior to non-music therapy in the treatment of pain, depression, and improvement of quality of life in fibromyalgia patients. However, due to the low quantity and quality of the included studies, a larger number and high-quality of RCTs are needed to confirm the beneficial effects of music therapy.

Salvanic acid B inhibits myocardial fibrosis through regulating TGF-ß1/Smad signaling pathway.

OBJECTIVE: Salvanic Acid B (Sal B) was proved to show significant effect against fibrosis and myocardial injury. This study aimed to investigate the protective effects and the mechanisms of Sal B on myocardial fibrosis. METHODS: The mice were randomly assigned to five groups: control group, model group, positive group, low-dose group, high-dose group. Hematoxylin-Eosin (HE) staining and Masson staining were used to assess the myocardial physiological changes and measure the myocardial fibrosis area. Expression of transforming growth factor-beta (TGF-ß), drosophila mothers against decapentaplegic (Smad)2, Smad3 and Smad7 were analyzed by immunohistochemistry and real-time PCR. On the other hand, mouse cardiac fibroblasts (CFs) cells were co-treated with 20 ng/mL TGF-ß1 and different concentrations of Sal B (5, 10, and 20 ng/mL) for 24 h. The cells morphology changes were assessed under a microscope, and the protein expressions induced by TGF-ß1 were detected by Western blot. RESULTS: Compared with the model group, myocardial collagen fibers decreased obviously with Sal B treatment (p < 0.05). Moreover, the expression of key signal molecules of the TGF-ß/Smads signaling pathway, including TGF-ß1, Smad2 and Smad3 proteins decreased, while the expression of Smad7 increased in Sal B treatment groups as compared to those of the model group (p < 0.05). On the other hand, results of CFs studies were also consistent with those animals. CONCLUSIONS: Sal B could inhibit the myocardial fibrosis process through regulating TGF-ß/Smads signal transduction pathways.

Zeylenone inhibits proliferation and promotes apoptosis in ovarian carcinoma cells via Janus kinase 2 / signal transducers and activators of transcription 3 pathways.

AIM: Ovarian cancer is the fifth common cancer in females. The aim of our study was to determine function of Zeylenone on cell viability and apoptosis of ovarian carcinoma SKOV3 cells. METHODS: Cell viability was measured by Cell counting kit-8 (CCK8) assay; Mitochondrial membrane potential (MMP) and apoptosis were detected by flow cytometry. The mRNA and protein levels of related factors were determined by Real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot, respectively. RESULTS: Cell viability was decreased by Zeylenone in a dose-dependent manner. Zeylenone with concentrations of 2.5, 5 and 10 µmol/L was used to treat ovarian carcinoma SKOV3 cells for 24 h in the following study. The loss of MMP and apoptosis were both significantly increased by Zeylenone. The mRNA and protein levels of cytochrome c (cyto c) and apoptosis inducing factor (AIF) in cytosol were increased by Zeylenone. The mRNA and protein levels of Caspase-3, Fas, Fasl and Bax were increased; while the expression of Bcl-2 was decreased by Zeylenone. The expression of (Janus family of tyrosine kinase) p-JAK and signal transducer and activator of transcription (p-STAT) was decreased significantly by Zeylenone. CONCLUSION: Zeylenone inhibited cell proliferation and promoted apoptosis in ovarian carcinoma cells. The JAK-STAT pathway was involved in this progress.

Efficacy and safety investigation of Kuntai capsule for the add-back therapy of gonadotropin releasing hormone agonist administration to endometriosis patients: a randomized, double-blind, blank- and tibolone-controlled study.

BACKGROUND: As a Chinese Traditional Medicine product, Kuntai capsule could improve the peri-menopausal symptoms in postmenopausal women. But it is still not clear whether Kuntai capsule has a good effect on alleviating peri-menopausal symptoms induced by gonadotropin releasing hormone agonist (GnRH-a) treatment. The purpose of this study was to investigate the clinical effectiveness and safety of Kuntai capsule, on peri-menopausal symptoms in endometriosis (EMS) patients, with postoperative GnRH-a treatment. METHODS: Ninety EMS ovarian cyst women with postoperative GnRH-a administration were enrolled in the study, and were randomly divided into Kuntai group, Tibolone group, or blank Control group. The therapeutic strategy in Kuntai group was 4 Kuntai capsules tid,po for 12 weeks after the first GnRH-a injection, while Tibolone 2.5 mg qd, po for 12 weeks in Tibolone group. There was no drug addition in Control group. Climacteric complaints were evaluated by Kupperman menopausal index (KMI) and hot flash/sweating score. Liver and renal functions, lipid profile, serum sex hormone levels and endometrial thickness were measured, and the frequency of adverse events in Kuntai and Tibolone groups was recorded. RESULTS: (1) Before GnRH-a therapy, the baseline parameter results were comparable in the three groups (P > 0.05). (2) After GnRH-a therapy, KMI and hot flash/sweating scores in all the three groups increased significantly (P < 0.05). At the 4 th week after GnRH-a therapy, KMI and hot flash/sweating score results were as follows: Control group > Kuntai group > Tibolone group (P < 0.05); at the 8 th and 12 th week after GnRH-a therapy, KMI and hot flash/sweating score in Control group were significantly higher than the other two groups (P < 0.05), and no significant difference was identified between Kuntai and Tibolone group (P > 0.05). (3) No statistical change took place in the liver and renal functions and lipid profile in all the three groups after the treatment (P > 0.05). (4) The posttherapeutic serum follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2) level and endometrial thickness decreased significantly in all the three groups (P < 0.05). After therapy, serum E2 level in Tibolone group was obviously higher than the other two groups (P < 0.05), while FSH and LH levels were obviously lower (P < 0.05). (5) The incidence of vaginal bleeding, breast distending pain in Tibolne group was obviously higher than Kuntai group (P < 0. 05). CONCLUSIONS: Kuntai capsule is effective on the peri-menopausal symptoms induced by postoperative GnRH-a administration to EMS patients, although its clinical effect might be a few weeks later than Tibolone. Kuntai capsule might be a little safer than Tibolone tablet.

[Rehmanniae Radix and Rehmanniae Radix Praeparata Ameliorates Renal Interstitial Fibrosis Induced by Unilateral Ureteral Occlusion in Rats and Their Mechanism].

OBJECTIVE: To study the effects of Rehmanniae Radix and Rehmanniae Radix Praeparata on renal interstitial fibrosis (RIF) of obstructed kidneys in a unilateral ureteral obstruction (UUO) rat model and the mechanism. METHODS: 20 rats were randomly divided into four groups : sham operated group, UUO group, Rehmanniae Radix decoction group and Rehmanniae Radix Praeparata decoction group. The sham operated group and the UUO group were orally administered normal saline, the drug groups were orally administered 1.6 g/(kg x d) of Rehmanniae Radix decoction and Rehmanniae Radix Praeparata decoction for 14 days, respectively. Then the serum of rats were collected for measurements of Scr and BUN contents. Histological changes of kidneys were observed by HE and Masson staining. The expression of transforming growth factor-ß1, (TGF-ß1), α-smooth muscle actin (α-SMA) and type I collagen (Collagen-I) were detected by Western blot method. RESULTS: Compared with model group, the contents of Scr and BUN in rats serum of drug groups were significantly decreased (P < 0.05), the sclerosis of glomerulus was ameliorated, the degree of saccular dilatation and the damage of tubules were alleviated, collagen distribution and interstitial fibrosis was obviously improved,while the expressions of TGF-ß1, α-SMA and Collagen-I were decreased. Compared with Rehmanniae Radix Praeparata decoction group,the contents of Scr and BUN in rats serum of Rehmanniae Radix decoction group were lower, the decrease of collagen distribution and interstitial fibrosis were more obviously, while the expression of α-SMA was significantly decreased (P < 0.05). CONCLUSION: The effect of Rehmanniae Radix is more powerful than that of Rehmanniae Radix Praeparata on attenuating interstitial fibrosis,which may relative to downregulating the expressions of TGF-ß1, α-SMA and Collagen-I.

Efficacy and safety of remifemin on peri-menopausal symptoms induced by post-operative GnRH-a therapy for endometriosis: a randomized study versus tibolone.

BACKGROUND: The aim of this study was to investigate clinical efficacy and safety of Remifemin on peri-menopausal symptoms in endometriosis patients with a post-operative GnRH-a therapy. MATERIAL AND METHODS: We treated 116 women who had endometriosis with either Remifemin (n=56) 20 mg bid po or Tibolone (n=60) 2.5 mg qd po for 12 weeks after GnRH-a injection. The efficacy was evaluated by Kupperman menopausal index (KMI), and hot flash/sweating scores. The safety parameters such as liver and renal functions, lipid profile, endometrial thickness, and serum sex hormone level, as well as the incidence of adverse events were recorded. RESULTS: (1) After GnRH-a therapy, KMI and hot flash/sweating scores in both groups increased significantly (P<0.05) but we found no significant difference for KMI (2.87±1.40 for Remifemin and 2.70±1.26 for Tibolone) and hot flash/sweating scores (0.94±1.72 for Remifemin and 1.06±1.78 for Tibolone) between the 2 groups (P>0.05). (2) No statistical change was observed in liver or renal functions and lipid profile in both groups before and after the treatment (P>0.05). The post-therapeutic serum FSH, LH, and E2 level and endometrial thickness decreased remarkably in both groups (P<0.05). E2 level in the Remifemin group was obviously lower than that in the Tibolone group (P<0.05), and FSH and LH levels were strongly higher (P<0.05). No significant difference in thickness were found in either group (P>0.05). The Remifemin group had far fewer adverse events than the Tibolone group (P<0. 05). CONCLUSIONS: Compared with Tibolone, Remifemin had a similar clinical efficacy and was safer for the peri-menopausal symptoms induced by GnRH-a in endometriosis patients.

[Effect of Epimedium extract on osteoprotegerin and RANKL mRNA expressions in glucocorticoid-induced femoral head necrosis in rats].

OBJECTIVE: To investigate the effect of glucocorticoid on the expression levels of osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) mRNAs in rat femoral head and the antagonistic effect of Epimedium, and explore the mechanism of Epimedium in preventing glucocorticoid-induced femoral head necrosis. METHODS: Forty-eight adult SD rats were randomized into glucocorticoid group, Epimedium group and control group. In the former two groups, the rats received intramuscular injection of 12.5 mg prednisolone twice a week, and in Epimedium group, additional 1 ml/100 g aqueous Epimedium extract (equivalent to 0.1 g/ml of the crude drug) was administered intragastrically once daily. The control group received only intramuscular saline injection. After 4 weeks of treatment, osteonecrosis of the left femoral head was detected by HE staining, and the right femoral head was sampled for detection of OPG and RANKL mRNA expressions using real-time quantitative PCR. RESULTS: In glucocorticoid, Epimedium and control groups, the mortality rate of the rats was 12.5% (2/16), 6.25% (1/16), 0 (0/16), and femoral head necrosis occurred at a rate of 71.43% (10/14), 26.67% (4/15), and 0 (0/16), respectively. In glucocorticoid group, the expression level of OPG mRNA was significantly lower, RANKL expression significantly higher, and OPG/RANKL ratio significantly lower than those in Epimedium and control groups (P<0.05). OPG, RANKL and their ratios showed no significant differences between Epimedium group and the control group. CONCLUSION: Epimedium can prevent glucocorticoid-induced femoral head necrosis probably by antagonizing glucocorticiod-induced abnormal expressions of OPG and RANKL mRNA.

Protection of chronic renal failure by a polysaccharide from Cordyceps sinensis.

A water-soluble polysaccharide (CPS-2), isolated from the cultured Cordyceps sinensis, was obtained by hot-water extraction, anion-exchange and gel permeation chromatography. Its structural characteristics were investigated by PMP pre-column derivation, periodate oxidation, methylation analysis, FTIR and NMR spectroscopy. CPS-2 was found to be mostly of alpha-(1-->4)-D-glucose and alpha-(1-->3)-D-mannose, branched with alpha-(1-->4,6)-D-glucose every twelve residues on average. CPS-2 had a molecular weight of 4.39x10(4) Da. The protective effect of CPS-2 on the model of chronic renal failure was established by fulgerizing kidney. The changes in blood urea nitrogen and serum creatinine revealed that CPS-2 could significantly relieve renal failure caused by fulgerizing kidney.