Explorating the mechanism of Huangqin Tang against skin lipid accumulation through network pharmacology and experimental validation.

ETHNOPHARMACOLOGICAL RELEVANCE: Huangqin Tang (HQT), a famous prescription with the effect of clearing pathogenic heat and detoxifying, was first recorded in "Treatise on Typhoid and Miscellaneous Diseases". It has proved that HQT has good anti-inflammatory and antioxidant effects and can improve acne symptoms clinically. However, the study on the regulation of HQT on sebum secretion which is one of the inducements of acne is not enough. AIM OF THE STUDY: This paper aimed to investigate the mechanisms of HQT in the treatment of skin lipid accumulation by network pharmacology and validating the results via in vitro experiments. MATERIALS AND METHODS: Network pharmacology was employed to predict the potential targets of HQT against sebum accumulation. Then, the palmitic acid (PA)-induced SZ95 cell model was established to evaluate the effect of HQT on lipid accumulation and anti-inflammation, and the core pathways predicted by network pharmacology were verified in cell studies. RESULTS: 336 chemical compounds and 368 targets in HQT were obtained by network pharmacology, of which 65 targets were related to sebum synthesis. 12 core genes were revealed by protein-protein interaction (PPI) network analysis. Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment results suggested that AMP-activated protein kinase (AMPK) signaling pathway might play a crucial role in regulating lipogenesis. In vitro experiments, HQT suppressed lipid accumulation, downregulated the expressions of sterol-regulatory element binding protein-1 (SREBP-1) and fatty acid synthase (FAS), and upregulated AMPK phosphorylation. Furthermore, AMPK inhibitor reversed HQT-mediated sebosuppressive effect. CONCLUSION: The results disclosed that HQT ameliorates lipogenesis in PA-induced SZ95 sebocytes partially through the AMPK signaling pathway.

Hydrolyzed Conchiolin Protein (HCP) Extracted from Pearls Antagonizes both ET-1 and α-MSH for Skin Whitening.

Pearl powder is a famous traditional Chinese medicine that has a long history in treating palpitations, insomnia, convulsions, epilepsy, ulcers, and skin lightining. Recently, several studies have demonstrated the effects of pearl extracts on protection of ultraviolet A (UVA) induced irritation on human skin fibroblasts and inhibition of melanin genesis on B16F10 mouse melanoma cells. To further explore the effect we focused on the whitening efficacy of pearl hydrolyzed conchiolin protein (HCP) on human melanoma MNT-1 cells under the irritation of alpha-melanocyte-stimulating hormone (α-MSH) or endothelin 1 (ET-1) to evaluate the intracellular tyrosinase and melanin contents, as well as the expression levels of tyrosinase (TYR), tyrosinase related protein 1 (TRP-1), and dopachrome tautomerase (DCT) genes and related proteins. We found that HCP could decrease the intracellular melanin content by reducing the activity of intracellular tyrosinase and inhibiting the expression of TYR, TRP-1, DCT genes and proteins. At the same time, the effect of HCP on melanosome transfer effect was also investigated in the co-culture system of immortalized human keratinocyte HaCaT cells with MNT-1. The result indicated that HCP could promote the transfer of melanosomes in MNT-1 melanocytes to HaCaT cells, which might accelerate the skin whitening process by quickly transferring and metabolizing melanosomes during keratinocyte differentiation. Further study is needed to explore the mechanism of melanosome transfer with depigmentation.

Effects of polysaccharides from Yingshan Yunwu tea on free amino acids, flavor nucleotides and antioxidant abilities in chickens.

Tea polysaccharides possess a variety of physiological activities including anti-oxidant, anti-cancer, anti-diabetic, immunomodulatory, hypolipidemic, and cation chelating ability, which have been proved a promising feed additive. Our study aimed to investigate the effects of polysaccharides from Yingshan Yunwu tea (GTPS) on free amino acids, flavor nucleotides and antioxidant ability in chickens. A total of 200 chickens were randomly divided into to 4 groups. Chickens were fed chicken basal diet with GTPS (200, 400 and 800 mg/kg). The results showed that GTPS increased body weight, average daily gain, and average daily feed intake in chickens. Moreover, GTPS increased the total amount of free amino acids of meat, and increased the content of histidine, leucine, serine, glutamic acid and alanine. GTPS also increased contents of inosine monophosphate and guanylic monophosphate, which improved the meat flavor of chickens. In addition, GTPS significantly increased (P < 0.05) contents of GSH-Px, SOD and T-AOC, and reduced content of MDA. It also increased Nrf2, NQO-1 and HO-1 mRNA expressions, and decreased Keap1expression. GTPS increased Nrf2 and HO-1 protein levels, and decreased Keap1 level. The above findings indicated that GTPS could be a promising natural feed additive in poultry industry.

Clinical Efficacy of Modified Qilang Prescription in Treatment of Drug-dependent Constipation with Qi and Yin Deficiency and Its Effect on MTL， VIP， 5-HT， and 5-HT4R in Peripheral Blood / 中国实验方剂学杂志

Objective:To investigate the curative efficacy of modified Qilang prescription on drug-dependent constipation with Qi and Yin deficiency and the effects on serum vasoactive intestinal peptide （VIP）， motilin （MTL）， 5-hydroxytryptamine （5-HT）， and 5-hydroxytryptamine 4 receptor （5-HT4R）. Method:A total of 160 patients diagnosed with drug-dependent constipation were randomly divided into a treatment group （<italic>n</italic>=80， Qilang prescription） and a control group （<italic>n</italic>=80， lactulose oral solution）. The treatment lasted for eight weeks. Changes in clinical symptoms， traditional Chinese medicine （TCM） syndrome， and serum VIP， MTL， 5-HT， and 5-HT4R before and after treatment were observed. The clinical efficacies of the two groups were compared. An eight-week follow-up was carried out for the observation of recurrent rate and TCM syndrome. Result:The overall response rate of the treatment group （90.91%） was higher than that （75.00%） of the control group<italic> </italic>（<italic>Z</italic>=-6.514，<italic>P</italic><0.05）. There was no significant difference in serum VIP， MTL， 5-HT， and 5-HT4R between the two groups before treatment. After treatment for eight weeks， both groups showed reduced serum VIP level as compared with those before treatment， and the treatment group was inferior to the control group （<italic>P</italic><0.05）. The serum MTL levels of the two groups were both higher than those before treatment （<italic>P</italic><0.05）， and the treatment group was superior to the control group （<italic>P</italic><0.05）. After treatment， the level of 5-HT in the treatment group was higher than that in the control group （<italic>P</italic><0.05）. The post-treatment 5-HT4R level in the treatment group slightly increased （<italic>P</italic><0.05）， but no significant difference in 5-HT4R levels between the two groups after treatment was observed. During the eight-week follow-up， the recurrence rate in the treatment group was significantly lower than that in the control group at the 2nd and 4th weeks （<italic>P</italic><0.05）. There was no significant difference in the recurrence rate between the treatment group ［57.14% （40/70）］ and the control group ［64.81% （35/54）］ after eight weeks. Conclusion:Modified Qilang prescription was superior to lactulose in the short- and mid-term efficacy on drug-dependent constipation with Qi and Yin deficiency. No significant difference in the long-term efficacy was observed. The underlying therapeutic mechanism might be related to the regulation of serum VIP， MTL， 5-HT， and 5-HT4R levels.

Clinical study of XiangShaLiuJunZi decoction combined with S-1 as maintenance therapy for stage III or IV gastric carcinoma and colorectal carcinoma.

INTRODUCTION: S-1, a new oral fluorouracil chemotherapeutical drug, has been increasingly used in clinical maintenance after first-line chemotherapy for stage III or IV gastric carcinoma (GC) and colorectal carcinoma (CRC) for its own advantages. XiangshaLiujunzi Decoction (XSLJZD), a classic traditional Chinese medicine (TCM) formula with effects of alleviating the adverse reactions of chemotherapy and improving the quality of life of cancer patients has been gradually confirmed, with no more reports about the maintenance therapy mode of combination of chemotherapeutic drugs and TCM. We designed the study of XSLJZD combined with S-1 in the maintenance therapy of Stage III or IV GC and CRC, and hoped that this research program will go further and comprehensively evaluate its efficacy and safety. OBJECTIVES: The aim of this study was to determine the efficacy and safety of XSLJZD combined with S-1 in the maintenance therapy of stage III or IV GC and CRC. METHODS: This study is an open, single-center, randomized study. Patients with stage III or stage IV GC and CRC will be randomized (1:1) into S-1group, S-1 combined with XSLJZD group for 5 years of maintenance therapy. The primary endpoint was progression-free survival, and secondary end point was overall survival and Quality of Life Assessment (QOLA), which include an improvement in symptoms before and after treatment, Karnofsky Performance Status, and adverse events assessment. DISCUSSION: This study will provide meaningful clinical information about the combination of chemotherapeutic drugs S-1 with TCM in the maintenance therapy of stage III or IV GC and CRC. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR-INR-16008575.

Effects of polysaccharides from Yingshan Yunwu tea on meat quality, immune status and intestinal microflora in chickens.

The present study was aimed to investigate the effects of the addition of Yingshan Yunwu green tea polysaccharide conjugates (GTPC) on meat quality, immune response and gut microflora in chickens. A total of 200 chickens with average initial body weight were randomly allotted to 4 groups. Intestinal samples were collected at the end of experiment for bacterial culture and microbial community analysis by 16S rDNA gene sequencing using Illumina MiSeq. Chicken breast muscle and serum were also sampled for analysis of meat quality and immune function. The results showed that dietary GTPC addition increased (P < 0.05) chicken breast muscle pH and redness-greenness (a*) value and decreased (P < 0.05) the values of lightness (L*), yellowness-blueness (b*), hardness, toughness and adhesiveness. In addition, dietary supplementation of GTPC increased (P < 0.05) the weight of thymus and bursa and serum concentrations of IgA and IgG. Furthermore, of the 10 bacterial phyla, the predominant taxa across all sampling time-points were Bacteroidetes, Firmicutes, Proteobacteria, and Deferribacteres, representing >97% of all sequences. GTPC increased the abundance of Bacteroidetes and Lactobacillus, and decreased the abundance of Proteobacteria. These findings provided some references of the application of GTPC in the poultry industry.

Investigation of Chemical Composition, Antioxidant Activity, and the Effects of Alfalfa Flavonoids on Growth Performance.

The flavonoids were extracted from alfalfa using ethanol assisted with ultrasonic extraction and purified by D101 macroporous resin column chromatography. The chemical composition and content of ethanol elution fractions (EEFs) were assessed by ultrahigh-performance liquid chromatography and hybrid quadrupole time of flight mass spectrometry (UHPLC-Q-TOF-MS) and aluminum nitrate-sodium nitrite-sodium hydroxide colorimetric method. The in vitro antioxidant activity of two EEFs was conducted by scavenging DPPH free radical, and the main antioxidants of 75% EEFs were screened using DPPH-UHPLC. Moreover, the in vivo antioxidant activity of 75% EEFs and the growth performance of broilers were studied. The results showed that the content of 30% and 75% EEFs was 26.20% and 62.57%. Fifteen compounds were identified from 75% EEFs, and five of them were reported in alfalfa for the first time. The scavenging activity of 75% and 30% EEFs (200 µg/mL) against DPPH was 95.51% and 78.85%. The peak area of 5,3',4'-trihydroxyflavone and hyperoside was decreased by 82.69% and 76.04%, which exhibited strong scavenging capacities. The total antioxidant capacity (T-AOC), superoxide dismutase (SOD), and glutathione peroxidase (GSH-PX) level of three treated groups against the normal control group (NC) fed with basal diet significantly increased by 3.89-24.49%, 0.53-7.39%, and 0.79-11.79%, respectively. While the malondialdehyde (MDA) decreased by 0.47-18.27%. Compared with the NC, the feed to gain ratio (F : G) of three treated groups was lowered by 2.98-16.53% and survival rate of broilers significantly increased. Consequently, 75% EEFs extracted from alfalfa exhibited powerful antioxidant activities and might be a potential feed additive to poultry and livestock.

You-Gui-Yin improved the reproductive dysfunction of male rats with chronic kidney disease via regulating the HIF1α-STAT5 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: You-Gui-Yin (YGY) is a famous Chinese traditional medicine compound that has been used to treat renal function diseases for more than 300 years. It is recorded in Jing Yue Quanshu, which was written by a famous medical scientist named Jiebing Zhang in the Ming Dynasty. AIM OF THE STUDY: Reproductive dysfunction is one of the most serious complications of chronic kidney disease (CKD). The aim of this study was to observe the effect of You-Gui-Yin (YGY) on reproductive dysfunction of male rats with adenine-induced CKD and to determine if any effects occurred via regulation of the HIF1α-STAT5 pathway. MATERIALS AND METHODS: UPLC-Q-TOF-MS was used to detect the main medicinal components and conduct quality control of YGY. A total of 60 rats were randomly divided into 2 groups: the NC group (10 rats) and the CKD model group (50 rats). The CKD model rats was established by administration of adenine 150 mg kg-1 orally for 14 days. After that, the CKD rats were randomly divided into 5 groups: the CKD group, YGY (10 g kg-1 group, 20 g kg-1 group, 40 g kg-1 group) and the GUI-LU-ER-XIAN-JIAO (GL) 10 g kg-1 group with 10 rats in each group. From the 15th day to the 45th day rats were given 150 mg kg-1 adenine orally every other day to maintain the model (except in the NC group). The YGY groups and the GL group were orally administered the relevant drug once per day for 30 days. The NC group and the CKD group were orally administered an equal volume of normal saline for 30 days. On the 45th day, the rats' sexual behavior index was tested. On the 46th day, the rats were sacrificed. Biochemical indexes, histopathological changes of the kidneys and testes, sperm morphology, sperm abnormality rate, and key proteins in the HIF1α-STAT5 pathway in the kidney and testis were detected. RESULTS: Thirteen components in the YGY extract were identified by UPLC-Q-TOF-MS for quality control of the YGY extract. The results of the biochemical and physiological tests validated the success of inducing CKD accompanied by reproductive dysfunction in rats. YGY significantly retarded the CKD progression and improved the hormone levels of male CKD rats. Sexual behavior tests showed YGY can significantly improve CKD rats' sexual function. In addition, the pathological changes of the kidney and testis, sperm abnormality rate and sperm morphological abnormalities of the CKD rats were reduced by YGY. Furthermore, decreased expression of HIF1α and EPO, and increased expression of p-EPOR (Tyr368), p-JAK2 (Tyr570) and p-STAT5 (Ser725) were observed in the kidney and the testis of the CKD rats. The YGY extract dramatically increased the expression of HIF1α and EPO, and decreased the expression of p-EPOR (Tyr368), p-JAK2 (Tyr570) and p-STAT5 (Ser725) to regulate key proteins in the HIF1α-STAT5 pathway of the kidney and testis. CONCLUSIONS: YGY has obvious reversal effects on the abnormal symptoms of adenine-induced CKD and the abnormal symptoms of rats with hypothyroidism and male reproductive hypotension. Its mechanism is related to its ability to regulate the HIF1α-STAT5 pathway.

Chemical Composition and Antioxidant Activities of Polysaccharides from Yingshan Cloud Mist Tea.

The study was designed to investigate the chemical composition and antioxidant activities of polysaccharides from Yingshan Cloud Mist Tea. The chemical composition of green tea polysaccharides (GTPS) was analyzed by Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscope (SEM), thermogravimetric (TGA), gas chromatograph (GC), and high-performance gel-permeation chromatography (HPGPC). Then, the antioxidant activities in vitro of GTPS, effects of GTPS on body weight, and the antioxidant activities in chickens were studied. The results showed that GTPS were composed of rhamnose (Rha), arabinose (Ara), xylose (Xyl), mannose (Man), glucose (Glu), and galactose (Gal) in a molar ratio of 11.4 : 26.1 : 1.9 : 3.0 : 30.7 : 26.8 and the average molecular weight was 9.69 × 104 Da. Furthermore, GTPS exhibited obvious capacity of scavenging DPPH radical, hydroxyl radical, and superoxide radical and enhanced the ferric-reducing power in vitro. Last, GTPS significantly increased the body weight of chickens, enhanced the T-AOC, SOD, and GSH-Px level, and decreased the content of MDA in chickens. The results indicated that GTPS might be a kind of natural antioxidant, which had the potential application in feed industry.

First record of Leptospira and Blastocystis infections in captive flying squirrels (Trogopterus xanthipes) from Enshi County, China.

In traditional Chinese medicine, the feces of flying squirrels have long been used to promote blood circulation and relieve bodily stasis. However, the excrement of flying squirrels may harbor zoonotic agents that could be hazardous to public health. To understand the occurrence of bacterial and parasitic infections in this species, we investigated selected zoonotic pathogens including Leptospira and Blastocystis in the urine and feces of flying squirrels in China. Urine and fecal samples from flying squirrels were collected from a family-owned flying squirrel farm located in Enshi County, Hubei Province in China. Leptospira and Blastocystis DNA was extracted from the urine and feces of flying squirrels, and used as targets for PCR amplification, using different specific primers. PCR amplification and DNA sequencing showed that 4.4% (3/69) of flying squirrels were positive for Leptospira, while 30.4% (21/69) of the animals were positive for Blastocystis. Notably, 1.4% (1/69) of flying squirrels were found to be co-infected with Leptospira and Blastocystis. Sequence analyses allowed for the detection of 3 Blastocystis subtypes (ST1, ST3 and ST13), and mixed infections of Blastocystis subtype 1 and subtype 3 were found in 4.4% (3/69) of flying squirrels. Phylogenetic analysis of the 16S ribosomal RNA gene (rrs2), the flagellin B gene (flaB), and outer membrane lipoprotein lipL32 gene (LipL32) sequences indicated that the Leptospira species detected in the study was L. interrogans. We concluded that flying squirrels from central China were infected with Leptospira and Blastocystis, suggesting that these animals can be a source of infection for their owners, and using fresh excrement from this animal as traditional medicine could be risky to human health. To the best of our knowledge, this is the first report of Leptospira and Blastocystis infection in flying squirrels from Enshi County, China. Our findings provide new data on the epidemiology of these pathogens in this region.

Aqueous extract from You-Gui-Yin ameliorates cognitive impairment of chronic renal failure mice through targeting hippocampal CaMKIIα/CREB/BDNF and EPO/EPOR pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: You-Gui-Yin (YGY) is a traditional Chinese recipe used for reinforcing kidney essence which is recorded in Jingyue Quanshu written by Zhang Jingyue in Ming dynasty. According to traditional Chinese medicine theory, kidney essence is associated with brain and without sufficient kidney essence, cognitive impairment may occur. AIM OF THE STUDY: In this study, we aimed to investigate the effect of YGY extract on cognitive impairment of chronic renal failure (CRF) mice and explore the mechanisms involved. MATERIALS AND METHODS: Aqueous extract of YGY was prepared from crude drugs and was quality controlled by high-performance liquid chromatography (HPLC). CRF was induced by 0.2% adenine in mice and CRF mice were intragastrically administered with 1.5 g kg-1, 3.0 g kg-1, and 6.0 g kg-1 of YGY extract. Mice were identified with CRF by determining several biochemical and physiological indexes, including creatinine clearance rate, serum creatinine, serum urea nitrogen, serum Ca, serum P, serum Mg, body weight and body temperature. Morris water maze and novel object recognition tests were conducted for evaluation of cognitive function. In addition, changes of CaMKIIα/CREB/BDNF and EPO/EPOR pathways in hippocampus were examined by detecting the protein expressions of CaMKIIα, p-CaMKIIα (Thr286), CREB1, p-CREB1 (Ser133), BDNF, EPO, EPOR, p-EPOR (Tyr485), STAT5, and AKT1 using western blotting assays. Also, the primary EPO-producing cells in brain (i.e. astrocytes) and EPO expression regulator HIF-2α were checked by fluorescence microscopy and western blotting assay, respectively. RESULTS: Nine components in YGY extract were figured out and monitored with their contents by HPLC for the quality control of YGY extract. Biochemical and physiological measurements validated the success of induction of CRF in mice, and YGY extract significantly retarded the CRF progression and ameliorated the CRF-induced cognitive impairment. The behavioral tests showed that compared with normal control mice, CRF mice had impaired cognitive function. However, treatment of YGY extract significantly ameliorated the cognitive impairment of CRF mice. Additionally, decreased expressions of hippocampal CaMKIIα, p-CaMKIIα (Thr286), CREB1, p-CREB1 (Ser133), and BDNF were observed in the hippocampus of CRF mice, but YGY extract significantly restored these protein expressions. Moreover, hippocampal EPO, EPOR, p-EPOR (Tyr485), STAT5, AKT1, and HIF-2α, as well as the number of astrocytes in CA1 zone of hippocampus were also decreased in CRF mice, while YGY extract prominently promoted the expressions of these proteins and increased the number of astrocytes. CONCLUSIONS: All the data in this study suggested that YGY extract ameliorated the cognitive impairment of CRF mice, and this amelioration was related to up-regulating the CaMKIIα/CREB/BDNF and EPO/EPOR pathways.

[Changes of EPO in rats with chronic renal failure and low immunity and reversal effects of Yougui Yin and exogenous EPO].

The aim of this paper was to observe the changes of EPO in rats with chronic renal failure and low immunity induced by adenine and to investigate the reversal effect of Yougui Yin(YGY)and exogenous EPO.SD rats were randomly divided into normal control group(n=20)and adenine-model group(n=90).The adenine-model group rats were given with adenine 150 mg·kg~(-1)for 14days by gavage administration,and then randomly divided into 8 groups as follows:model group(n=20),YGY groups(10,20,40 g·kg~(-1),10 in each group),rh EPO group(500,1 000,1 500 IU·kg~(-1),10 in each group),and Guilu Erxian Gao 10 g·kg~(-1)group(positive control group,n=10).From the 15th day,every group except normal control group received 150 mg·kg~(-1)adenine by gavage administration once every two days to maintain the model.Meanwhile,the rats in each YGY group and Guilu Erxian Gao group received corresponding drugs by gavage administration once a day for 30 days.The rats in rh EPO groups were subcutaneously injected with rh E-PO once every 3 days for 30 days.On day 46,rats were anesthetized to take blood and then sacrificed.The serum levels of creatinine,urea,glandular hormone,immunoglobulin,complement and interleukin,the proportion of T cells in the spleen,the killing rate of NKcells and the proliferative capacity of spleen cells were measured.Western blot was used to detect the key proteins in JAK2-STAT5 and NF-κB pathways mediated by EPO in kidney and spleen.As compared with the normal control group,the serum levels of CREA and UREA were increased significantly and the serum levels of ACTH,T and T3 were decreased significantly in the model group rats,indicating that the functions of kidney,adrenal gland,gonad and thyroid in rats were decreased.At the same time,the serum levels of Ig A,Ig G,Ig M,C3,C4,IL-2 and IL-6 were significantly decreased,the proportion of CD4~+,CD4~+/CD8~+T cell subsets,the killing rate of NK cell and the proliferation ability of spleen lymphocyte in spleen of the model group rats were significantly declined,indicating that the immune function of model group rats was decreased,and the model of kidney deficiency immunodeficiency was successfully constructed.As compared with the model group,both YGY and rh EPO significantly reduced serum levels of CREA and UREA,significantly increased serum levels of ACTH,T,T3,T4,Ig A,Ig G,Ig M,C3,C4,IL-2,and IL-6,increased the proportion of CD4~+,CD4~+/CD8~+T cell subsets,the killing rate of NK cell and the proliferation ability of spleen lymphocyte in spleen.YGY could significantly increase the content of EPO in serum.Both YGY and rh EPO could regulate the expression of EPOR,p-JAK2/JAK2,STAT5,NF-κB p50,NF-κB p65 and NF-κB IκB of EPO-mediated JAK2-STAT5 and NF-κB pathways in kidney and spleen.EPO is an important factor in the chronic renal failure and low immunity induced by adenine in rats.Exogenous EPO and YGY have significant reversal effects for the model rats.The mechanism of YGY may be related to the up-regulation of EPO in serum and regulating the expression of key proteins in EPO-mediated JAK2-STAT5 and NF-κB pathways in kidney and spleen.The mechanism of exogenous EPO may be related to regulating the expression of the key proteins in EPO-mediated JAK2-STAT5 and NF-κB pathways in kidney and spleen.

Chemogenetic activation of glutamatergic neurons in the motor cortex promotes functional recovery after ischemic stroke in rats.

Ischemic stroke is a major cause of disability and mortality worldwide, while no unequivocally efficacious drug is currently available to treat post-stroke functional impairments. Animal and clinical investigations suggest that the motor cortex stimulation constitutes a particularly promising approach for promoting function recovery after stroke. However, the cell types and mechanisms involved in stimulation-induced recovery are not well understood. Here, we used chemogenetic technique to selectively activate glutamatergic neurons in the primary motor cortex and investigated whether activation of glutamatergic neurons in the primary motor cortex can promote functional recovery after ischemic stroke in rats. The results showed that chemogenetic activation of the motor cortex glutamatergic neurons significantly decreased the neurological deficit scores, as well as significantly increased the grip test scores and the hanging time. Moreover, the glutamatergic neuronal activation also significantly decreased the escape latencies, increased the swimming speed, target quadrant time, and numbers of crossing platform position in the Morris water maze test. These results demonstrate that selective activation of the glutamatergic neurons in primary motor cortex is sufficient to promote functional recovery after ischemic stroke, and may be of importance in understanding the neural cellular mechanisms underlying the motor cortex stimulation-induced functional recovery.

Electro-acupuncture Pretreatment at Zusanli (ST36) Acupoint Attenuates Lipopolysaccharide-Induced Inflammation in Rats by Inhibiting Ca2+ Influx Associated with Cannabinoid CB2 Receptors.

In this study, we aimed to investigate the effect of electro-acupuncture (EA) pretreatment at zusanli (ST36) acupoint on lipopolysaccharide (LPS)-induced endotoxemic rat model and explore the underlying molecular mechanisms. Rats were treated with EA at ST36 for 7 days before being subjected to LPS. Two hours post-LPS, samples such as serum, local acupoint tissues, and spleens were collected and processed for investigations including cytokine production, cytosolic calcium (Ca2+) concentration, Ca2+ influx, cannabinoid CB2 receptor (CB2R) expression, and TLR4/NF-κB signaling. Our results showed EA pretreatment significantly attenuated LPS-induced inflammatory cytokine production, such as TNF-α, IL-1ß, and IL-6. EA also enhanced CB2R expression, inhibited Ca2+ influx, and inactivated TLR4/NF-κB signaling, subsequently resulting in a substantial reduction of Ca2+ concentration. Importantly, CB2R antagonist AM630 effectively abrogated the suppressive effect of EA at ST36 on the endotoxemic rats, suggesting CB2R was involved in the anti-inflammatory effect of EA. EA pretreatment could enhance CB2R expression, inhibit Ca2+ influx, and inactivate TLR4/NF-κB signaling, which contributes to the alleviation of LPS-induced inflammation in rats.

First total synthesis of a new phenylpropanoid glycoside: natural cytotoxic compound from Cirsium japonicum.

Phenylpropanoid glycoside compound 1, the natural anti-tumor compound isolated from the erial parts of Cirsium japonicum, was first totally synthesized using easily available materials in short, convenient route with overall yield of 13.9%.

[Comprehensive regulation effect of traditional Chinese medicine on proliferation and differentiation of neural stem cells].

Since the discovery of neural stem cells(NSCs) in embryonic and adult mammalian central nervous systems, new approaches for proliferation and differentiation of NSCs have been put forward. One of the approaches to promote the clinical application of NSCs is to search effective methods to regulate the proliferation and differentiation. This problem is urgently to be solved in the medical field. Previous studies have shown that traditional Chinese medicine could promote the proliferation and differentiation of NSCs by regulating the relevant signaling pathway in vivo and in vitro. Domestic and foreign literatures for regulating the proliferation and differentiation of neural stem cells in recent 10 years and the reports for their target and signaling pathways were analyzed in this paper. Traditional Chinese medicine could regulate the proliferation and differentiation of NSCs through signaling pathways of Notch, PI3K/Akt, Wnt/ß-catenin and GFs. However, studies about NSCs and traditional Chinese medicine should be further deepened; the mechanism of multiple targets and the comprehensive regulation function of traditional Chinese medicine should be clarified.

[Simultaneous determination of ten major compounds including iridoid glycosides and phenolic acids in Pterocephalus hookeri by UPLC-PDA].

This study is to develop an UPLC-PDA method for determination of 10 major components in Pterocephalus. The UPLC-PDA assay was performed on a Waters Acquity UPLCR BEH C18（2.1 mm ×100 mm,1.7 µm）, and the column temperature was at 30 ℃. The mobile phase consists of water containing 0.2% phosphoric acid (A) and acetonitrile (B) in gradient elution at a flow rate of 0.4 mL•min⁻¹. The detection wave length was set at 237 and 325 nm, and the injection volume was 1 µL in the UPLC system. The linear range of 10 detected compounds were good (r≥0.999 7), and the overall recoveries ranged from 96.30% to 103.0%, with the RSD ranging from 0.72% to 2.9%. The method was simple, accurate and reproducible, which can be used for the simultaneous determination of the content of ten major components in P. hookeri.

[Action mechanism of total flavonoids of Hippophae rhamnoides in treatment of myocardial ischemia based on network pharmacology].

In this study, a network pharmacological screening method was adopted to further study the active ingredients and action mechanism of total flavonoids of Hippophae rhamnoides(TFH) for the treatment of myocardial ischemia. Firstly TCMSP database and PubChem database were searched, and then the data were combined with oral bioavailability and drug analysis to screen flavonoids of H.rhamnoides compounds. Then predictive analysis was conducted for the 7 screened compounds by ChemMapper server.The obtained potential targets were imported into MAS 3.0. Database, and KEGG database was also used for targets analysis and pathway analysis. Finally Cystoscope 3.3.0 software was used to draw "compounds-targets-pathway" network diagram. Virtual experiments predicted 68 potential targets and 60 signaling pathways, and 31 targets and 23 pathways of them were directly or indirectly associated with myocardial ischemia. The results showed that TFH played a synergistic rolemainly through the regulation of calcium signaling pathway, VEGF signaling pathway and gap junction signaling pathway, which was consistent with literature reports. These results indicated that it can enhance heart function, protect vascular endothelial cells, and fight against myocardial ischemia probably by regulating platelet aggregation, lipid metabolism, inflammation and other processes.

Simultaneous determination of ten major compounds including iridoid glycosides and phenolic acids in Pterocephalus hookeri by UPLC-PDA / 中国中药杂志

This study is to develop an UPLC-PDA method for determination of 10 major components in Pterocephalus. The UPLC-PDA assay was performed on a Waters Acquity UPLCR BEH C₁₈（2.1 mm ×100 mm,1.7 μm）, and the column temperature was at 30 ℃. The mobile phase consists of water containing 0.2% phosphoric acid (A) and acetonitrile (B) in gradient elution at a flow rate of 0.4 mL•min⁻¹. The detection wave length was set at 237 and 325 nm, and the injection volume was 1 μL in the UPLC system. The linear range of 10 detected compounds were good (r≥0.999 7), and the overall recoveries ranged from 96.30% to 103.0%, with the RSD ranging from 0.72% to 2.9%. The method was simple, accurate and reproducible, which can be used for the simultaneous determination of the content of ten major components in P. hookeri.

Comprehensive regulation of traditional Chinese medicine on proliferation and differentiation of neural stem cells / 中国药理学与毒理学杂志

Since the diccovery of neural stem cells (NSCs) in the embryonic and adult mammalian central nerous system, it provided novel ideas forneurogenesis as the potential of proliferation and differentiation of NSCs. One of the ways to promote the clinical application of neural stem cells (NSCs) is searching effective methods which regulate the proliferation and differentiation.This is also a problem urgently to be solved in medical field. Plenty of earlier studies have shown that traditional chinese medicine can promote the proliferation and differentiation of NSCs by regulating the related signaling pathway in vivo and in vitro. The reports of Chinese and foreign literatures on regulating the proliferation and differentiation of neural stem cells in recent ten years and their target and signaling pathways is analyzed in this review.The traditional chinese medicine regulate proliferation and differentiation of NSCs by the signaling pathways of Notch,PI3K/Akt, Wnt/β- catenin, and GFs. And, those signaling pathways have cross- talk in the regulation progress. Moreover, some traditional Chinese medicine, such as astragalus,has a variety of active ingredients to regulate proliferation and differentiation of NSCs through different signaling pathways. However, to accelerate the clinical application of neural stem cells, the studies aboutthe proliferation and differentiation of NSCs and Chinese medicine should be further deepened, the mechanism of multiple targets and the comprehensive regulation function of traditional Chinese medicine should be clarified.