Traditional Chinese Medicine Clinics Research Articles

Rosmarinic acid in combination with ginsenoside Rg1 suppresses colon cancer metastasis via co-inhition of COX-2 and PD1/PD-L1 signaling axis.

Metastasis of colorectal cancer (CRC) is a leading cause of mortality among CRC patients. Elevated COX-2 and PD-L1 expression in colon cancer tissue has been linked to distant metastasis of tumor cells. Although COX-2 inhibitors and immune checkpoint inhibitors demonstrate improved anti-tumor efficacy, their toxicity and variable therapeutic effects in individual patients raise concerns. To address this challenge, it is vital to identify traditional Chinese medicine components that modulate COX-2 and PD-1/PD-L1: rosmarinic acid (RA) exerts striking inhibitory effect on COX-2, while ginsenoside Rg1 (GR) possesses the potential to suppress the binding of PD-1/PD-L1. In this study we investigated whether the combination of RA and GR could exert anti-metastatic effects against CRC. MC38 tumor xenograft mouse model with lung metastasis was established. The mice were administered RA (100 mg·kg-1·d-1, i.g.) alone or in combination with GR (100 mg·kg-1·d-1, i.p.). We showed that RA (50, 100, 150 μM) or a COX-2 inhibitor Celecoxib (1, 3, 9 μM) concentration-dependently inhibited the migration and invasion of MC38 cells in vitro. We further demonstrated that RA and Celecoxib inhibited the metastasis of MC38 tumors in vitro and in vivo via interfering with the COX-2-MYO10 signaling axis and inhibiting the generation of filopodia. In the MC38 tumor xenograft mice, RA administration significantly decreased the number of metastatic foci in the lungs detected by Micro CT scanning; RA in combination with GR that had inhibitory effect on the binding of PD-1 and PD-L1 further suppressed the lung metastasis of colon cancer. Compared to COX-2 inhibitors and immune checkpoint inhibitors, RA and GR displayed better safety profiles without disrupting the tissue structures of the liver, stomach and colon, offering insights into the lower toxic effects of clinical traditional Chinese medicine against tumors while retaining its efficacy.

Cantharidin induces apoptosis of human triple negative breast cancer cells through mir-607-mediated downregulation of EGFR

BackgroundTriple negative breast cancer (TNBC) is a major subtype of breast cancer, with limited therapeutic drugs in clinical. Epidermal growth factor receptor (EGFR) is reported to be overexpressed in various TNBC cells. Cantharidin is an effective ingredient in many clinical traditional Chinese medicine preparations, such as Delisheng injection, Aidi injection, Disodium cantharidinate and vitamin B6 injection. Previous studies showed that cantharidin had satisfactory pharmacological activity on a variety of tumors. In this study, we aimed to study the therapeutic potential of cantharidin for TNBC treatment by targeting EGFR, and expound its novel regulator miR-607.MethodsThe effect of cantharidin on breast cancer in vivo was evaluated by 4T1 mice model. Then the effects of cantharidin on TNBC cells was assessed by the MTT, colony formation, and AnnexinV-PE/7AAD staining. Cantharidin acts on EGFR were verified using the cell membrane chromatography, RT-PCR, Western blotting, MTT, and so on. Mechanistic studies were explored by dual-luciferase report assay, RT-PCR, western blotting, and immunofluorescence staining assay.ResultsCantharidin inhibited TNBC cell growth and induce apoptosis by targeting EGFR. miR-607 was a novel EGFR regulator and exhibited suppressive functions on TNBC cell behaviors. Mechanistic study showed that cantharidin blocked the downstream PI3K/AKT/mTOR and ERK/MAPK signaling pathway.ConclusionOur results revealed that cantharidin may be served as a potential candidate for TNBC treatment by miR-607-mediated downregulation of EGFR.Graphical

Influence of Gegenqinlian decoction on pharmacokinetics and pharmacodynamics of saxagliptin in type 2 diabetes mellitus rats.

Gegenqinlian decoction (GQD) is a classic prescription of traditional Chinese medicine (TCM), which originated from Shanghanlun. The combination of GQD and hypoglycemic drugs (saxagliptin, Sax, metformin) is often used to treat Type 2 diabetes mellitus (T2DM) in TCM clinics. However, the herb-drug interactions (HDIs) between GQD and hypoglycemic drugs are still unclear. In order to determine the safety of the combination, we assessed the influences of GQD on the pharmacokinetics and pharmacodynamics of Sax in T2DM rats. The plasma concentration of Sax (5mg/kg) pretreated with GQD (freeze-dried powder, 1.35g/kg) or not was determined by high-performance liquid chromatography (HPLC), and pharmacokinetics parameters were calculated. The influence of GQD on the pharmacodynamics of Sax was investigated by detecting the levels of weight, (see abbreviations list) OGTT, TC, TG, LDL-C, HDL-C, FBG, FINS, HOMA-IR, QUICKI, AST, ALT, and the liver coefficient. The Cmax , AUC0-t ,and AUC0-∞ of Sax increased significantly in the combination group whether in normal or T2DM rats. The results of pharmacodynamics showed that the weight of rats in each treatment group increased. FBG, TC, TG, LDL-C, and HOMA-IR decreased, HDL-C, FINS, and QUICKI increased significantly (p<0.05) compared with the model control group. The result showed that the combination of GQD and Sax could not only improve the hypoglycemic effect but also increase the plasma exposure of Sax. The potential HDIs between GQD and Sax should be taken into consideration in clinics. Moreover, for the complexity of the human compared with experimental animals, as well as genetic differences, the in-depth study should be carried out to assess the uniformity of the pharmacokinetics and pharmacodynamics between rats and humans.

Total flavonoids of Hippophae rhamnoides L. improves type 2 diabetes symptoms in rats through down-regulating of the DAG/PRKCA/MAPK10/p65/TNF-α signalling pathway

Ethnopharmacological relevanceDry mature fruits of Hippophae rhamnoides L. (HRL), Elaeagnaceae, have traditional functions of invigorating spleen and improving spleen insufficiency. Traditional Chinese medicine (TCM) clinics have been proved that HRL is in favor of diabetes treatment. Modern pharmacological studies demonstrated that total flavones of Hippophae rhamnoides (TFH) are the main substance for HRL to develop anti-inflammation and anti-diabetes functions. However, chemical features, active ingredients and anti-diabetes pharmacological mechanism of HRL still remain unclear. Aim of the studyKey targets and metabolites in anti-type-II diabetes mellitus (T2DM) of TFH have been explored based on AGE-RAGE signaling pathway in diabetic complications. The anti-T2DM mechanism of TFH has been elaborated from comprehensive perspectives, including target prediction, metabolites, potential metabolic pathways, and so on. Materials and methodsIn this study, a qualitative test of chemical composition of HRL was carried out based on ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF-MS). The anti-T2DM targets and pathways of HRL were predicted through network pharmacological approach. The T2DM rat model was induced by high-fat and high-glucose diet combined with streptozotocin (STZ). The T2DM model was evaluated through fasting blood glucose level, body weight, serum biochemical indicators, insulin levels and homeostatic model assessment of insulin resistance. The key metabolic pathways were screened through the correlation between metabolites and key targets. Finally, the quantitative analysis of key targets and metabolites was verified through experiments. ResultsAfter TFH intervention, the fasting blood-glucose level of T2DM rats induced by high-fat and high-glucose diet combined with streptozotocin (STZ) was downregulated significantly, while body weight, serum liquid level, insulin levels and homeostatic model assessment of insulin resistance (HOMA-IR) were improved. According to ELISA, Western blotting (WB) and reverse transcriptase polymerase chain reaction (RT-PCR), TFH significantly downregulates expression levels of diglyceride (DAG)-activated protein kinase C (PRKCA), mitogen activated protein kinase 10 (MAPK10), human nuclear factor κB subunit p65 (NF-κB p65) and tumor necrosis factor-α (TNF-α) in pancreas of STZ-induced rats. ConclusionsTFH downregulates expressions of PRKCA, MAPK10 and p65 TNF-α as well as level of the key metabolite DA in the DAG/PRKCA/MAPK10/TNF-α/p65 pathways, improves lipid metabolism disorder, inhibits inflammatory response and thereby relieves symptoms of T2DM.

Study on the substance basis of the efficacy of eucommiae cortex before and after salt processing for the treatment of kidney-yang deficiency syndrome based on the spectrum-effect relationship

Ethnopharmacological relevanceKidney-Yang deficiency syndrome (KYDS) is one of the common diseases of the elderly and closely related to the ageing of the body, it has a major impact on the quality of life of the patient. Eucommiae Cortex (EC) is the dried bark of Eucommia ulmoides Oliv. Which has the effect of tonifying the liver and kidneys, strengthening the muscles and bones. In Traditional Chinese Medicine clinics, EC is commonly used in the treatment of KYDS, but the material basis for the improvement of its efficacy in treating KYDS after salt processing remains unclear. Aim of the studyThis study aimed to find the main active ingredients that could improve the treatment of KYDS efficacy of EC after salt processing. Materials and methodsFirstly, the fingerprints of raw and salt-processed EC were established to determine the common components by using HPLC, and then an experimental study on the treatment of KYDS efficacy was carried out to compare the difference in the efficacy between raw and salt-processed EC. Thirdly, the spectrum-effect relationship of chemical components and pharmacodynamic indexes was established by using Grey Relational Analysis and Entropy Method. Finally, the network pharmacology and molecular docking technique was used to verify the kidney tonifying effect of the active ingredients of EC. ResultsAccording to the results of the analysis of hormonal index levels on the hypothalamic-pituitary-target gland axis and the extent of renal lesions, the therapeutic effect of EC on KYDS was mainly reflected in the regulation of the Adrenocorticotropic hormone, Corticosterone in the hypothalamic-pituitary-adrenal axis and Tri-iodothyronine, Tetra-iodothyronine in the hypothalamic-pituitary-thyroid axis, moreover the therapeutic effect of salt-processed EC was stronger than that of raw EC. The pharmacologically active ingredients that improved its treatment of KYDS efficacy after salt processing were peak 1 (geniposidic acid), peak 2 (chlorogenic acid), peak 5 (geniposide), peak 6 (genipin), peak 7 (pinoresinol diglucoside) and peak 11 (hyperoside). Meanwhile, the results of network pharmacology and molecular docking showed that the 6 active ingredients could exert kidney tonic effects through multiple signaling pathways by acting on core targets such as AKT1 and PTGS2. ConclusionAs far as we known, this was the first time to establish and compare the spectrum-effect relationship between raw and salt-processed EC, which laid the foundation for the pharmacokinetics studies of EC and provided a reference for future EC studies.

Research on Changes and Response Strategies of Health Human Resource Demands in CHSC in the aftermath of the COVID-19 Pandemic

Community health service centers (CHSC) are the first line of defense for national health. In the post-epidemic era, CHSC need to effectively play the role of the grassroots "outpost." In addition to daily medical and public health work, they should also strengthen joint prevention and control to consolidate the achievements of epidemic prevention and control. Under the new situation, the demand for talent in CHSC has also changed, and the construction of its talent team faces many challenges. This article collects relevant materials and data to analyze the changes in the work content of health personnel in CHSC in the post-epidemic era, and analyzes the changes in talent demand and key problems under the new situation, providing strategies to strengthen the construction of talent teams in CHSC in the new era. Key problems in CHSC in the post-epidemic era include unreasonable structure of health personnel, insufficient allocation of health personnel, unclear rights and responsibilities, and rigid talent training models. To improve the professional level and governance ability of health personnel in CHSC, optimize the working environment of health personnel, and address the issue of scarce positions, strategies are proposed such as relaxing recruitment conditions for scarce positions, encouraging the establishment of traditional Chinese medicine clinics, fully leveraging social collaborative forces, promoting diversified training for the capacity building of grassroots health personnel, and establishing new talent development platforms.

Discovery of Elaphuri Davidiani Cornu-specific peptide biomarkers by peptidomics analysis-based method.

Elaphuri Davidiani Cornu (EDC) is the antler of the male Père David's deer, which has been reported to have multiple biological activities, and its use as a traditional Chinese medicine (TCM) in China has been known for thousands of years. However, EDC is difficult to distinguish from other related species-derived antlers in powder or extract form in TCM clinic use, such as Cervus elaphus Cornu (CEC) and Cervus nippon Cornu (CNC), both derived from Cervidae and easily confused with EDC. In this study, a strategy using peptidomics combined with mathematics set analysis was used to identify EDC-specific peptide biomarkers, and four specific peptide biomarkers (Pep-E1-E4) were identified and validated. Pep-E1, Pep-E3, and Pep-E4 could be exclusively detected in EDC samples, with relative peak areas of 0.298±0.060, 0.039±0.015, and 0.037±0.008, whereas Pep-E2 showed relative peak area of 0.516±0.101 in EDC, 0.132±0.026 in CEC, and 0.136±0.047 in CNC samples, respectively. These four peptides are applicable to distinguish EDC from CEC and CNC, which is of great significance for the quality control of EDC.

Trehalose and brassinolide enhance the signature ingredient accumulation and anti-oxidant activity in the hairy root cultures of Polygala tenuifolia Willd.

Polygala tenuifolia Willd. is a commonly used clinical traditional Chinese medicine with a variety of biological activities. Hairy root cultures of medicinal plants are considered as a source of active constituents for pharmaceutical industries. In this study, P. tenuifolia hairy root cultures (PTHRCs) were established by induction of four Rhizobium rhizogenes, including ATCC15834, LBA9402, C58C1 and ACCC10060. The contents of active ingredients such as polygalaxanthone III, 3′,6-disinapoylsucrose, onjisaponin B, onjisaponin F, polygalacic acid and senegenin were detected in the hairy roots by high performance liquid chromatography (HPLC). Forty-five day-old leaf disc of P. tenuifolia sterile seedlings were prepared for explants, the highest hairy root transformation rate reached 85.83 % by using R. rhizogenes C58C1 co-cultured for 3 d with an optical density of 1.5 at 600 nm, coupled with 200 µM acetosyringone added in the solid culture medium. Meanwhile, the conditions of PTHRCs were optimized for the xanthones, saponins, and oligosaccharides components production. The results showed that the dry weight of the hairy roots reached its maximum of 0.44 g/flask (9.26 fold than that of the control) under the optimal culture conditions: 6,7-V medium, 3 % sucrose (m/v), pH 5.8, and 6 week-old PTHRCs, and the six signature ingredients in the hairy roots accumulated massively under the same condition simultaneously. Furthermore, trehalose and brassinolide were found to significantly promote the biomass and active ingredients biosynthesis in the hairy root cultures. The content of polygalaxanthone III was 8.92 folds higher than the description in the Chinese Pharmacopoeia (2020 year version) induced by 10 µM trehalose, while 1 × 10−12 M brassinolide treatment promoted onjisaponin F accumulation at 33.63 mg/g (dry weight) in PTHRCs. In addition, total phenolics, flavonoids, and antioxidant activity of PTHRCs extracts were significantly increased induced by trehalose (5 µM) and brassinolide (1 ×10−10 M), respectively. This is the first report on the systematic construction of PTHRCs and trehalose and brassinolide as effective elicitors for polygalaxanthone III, 3′,6-disinapoylsucrose, onjisaponin B, onjisaponin F, polygalacic acid and senegenin production in PTHRCs. The results demonstrated that PTHRCs can be used to produce active constituents in pharmaceutical and nutraceutical fields.

Clinical Retrospective Analysis of Cold and Heat Diagnosis of Traditional Chinese Medicine by Application of Infrared Thermal Imaging Technology

Objective: Exploring the application of infrared thermal imaging technology in Traditional Chinese Medicine (TCM) diagnosis of cold and heat by comparing the cold and heat of TCM clinical dialectics with the cold and heat objectively measured by infrared thermal imaging technology. Methods: First, there were 77 patients from the Prevention and Treatment Center of Guangdong Hospital of TCM selected to analyze their clinical information retrospectively. Then, transforming the temperature index measured by infrared thermal imaging technology into the cold and heat deviation index, which can reflect the cold and heat of traditional Chinese medicine. Finally, a Correlation analysis was made between patients' cold and heat deviation index, and clinical symptoms, the type of cold and heat syndrome diagnosed by doctors. Results: The cold and heat deviation index of the outer, upper outer, and lower outer parts of the patients was significantly lower than that of the inner, upper inner, and lower inner parts of the patients and the difference in the mean values of the three groups was 0.06, 0.07 and 0.03, respectively. In all parts of the subjects, the coincidence rate of clinical dialectics of cold and cold and heat deviation index less than 0 (belonging to cold) was 70.17%. In patients with fatigue symptoms, the cold and heat deviation index of the lower inner part, the upper inner part, and the inner part was significantly higher than that of the lower outer part, the upper outer part, and the outer part. Conclusions: The pattern of human torso region division combined with the cold and heat deviation index can be used to reflect the quantitative understanding of cold and heat in the TCM clinic. Quantifying the variation of cold and heat according to the trend of torso regional temperature deviation can explain the pathogenesis of some elementary symptoms closely related to cold and heat. As a quantitative index of TCM cold and heat, the offset index can be proof for visualization, objectification, and quantification, combined with doctors' judgment, which can an effective auxiliary diagnostic means of TCM to a certain extent.

When Patients' Assessments of Treatment for Subjective Symptoms are At Odds with Authoritative Assessments in the Biomedical Literature: The Case of Patients Treated with Acupuncture for Low Back Pain in a Traditional Chinese Medicine Clinic in China (and Story of a Bewildered Chicken).

Assessments of treatments for 'subjective symptoms' are problematic and potentially contentious. These are symptoms without ascertainable pathophysiology, also referred to as 'medically unexplained.' Treatments of them may be assessed from different perspectives, and an assessment as seen from one perspective may be discrepant with an assessment as seen from another perspective. The observational study described in the paper represents one perspective. Patients in the study were treated with acupuncture for the subjective symptom of low back pain in a Traditional Chinese Medicine Clinic in China; acupuncture is a form of TCM, which is indigenous to China. Shortly after treatment began and six months afterward, patients reported 'clinically important improvements' on a variety of standard, cross-culturally validated outcome measures, including pain intensity, physical functioning, and emotional functioning; this assessment is consistent with numerous assessments of acupuncture in China and other Southeastern Asian countries. On the other hand, clinical trials represent another perspective from which to assess acupuncture. Although assessments based on trials are not uniform, several assessments based on them, including those published in journals such as Lancet and New England Journal of Medicine, conclude that acupuncture is not effective. These trials, however, were mainly situated in the U.S., western European countries, and other WEIRD (Western, Educated, Industrialized, Rich, Democratic) countries. This is notable, because the population of China, the indigenous context of acupuncture, is greater than populations of WEIRD countries combined. Patients' expectations of a treatment such as acupuncture and their prior familiarity with it vary among contexts, and patients' experiences of treatment outcomes may vary accordingly. In short, although clinical trials constitute a test of truth in biomedicine and inform authoritative assessments in WEIRD countries, they do not necessarily represent the truth from the perspective of those experiencing outcomes of especially indigenous treatments for subjective symptoms in non-WEIRD contexts.

Si-Ni-San reduces lipid droplet deposition associated with decreased YAP1 in metabolic dysfunction–associated fatty liver disease

Ethnopharmacological relevanceMetabolic dysfunction-associated fatty liver disease (MAFLD) is the most common chronic liver disease worldwide. However, its complex pathogenesis and lack of effective drugs for treating it present significant challenges. Si-Ni-San (SNS) is one of the representative formulas for treating patients with MAFLD in traditional Chinese medicine (TCM) clinics. According to our previous work, SNS reduces lipid droplet (LD) deposition in livers of mice with MAFLD. Aim of the studyTo elucidate the mechanism of SNS in reducing LD deposition in MAFLD. Materials and methodsFirst, LD areas were detected with Oil red O staining in HepG2 cells induced by oleic acid (OA). Cell Counting Kit-8 (CCK-8) assay was used to test cell viability after treatment with different concentrations of SNS serum. The expression of Yes-associated protein 1 (YAP1) was monitored by Western blot. Second, C57BL/6 mice were fed a high-fat diet (HFD) for 12 weeks and gavaged with SNS decoction during the 11th and 12th weeks. Then, the weight of the body and the liver was examined. LD numbers and their locations in the liver were detected by triglyceride (TG) assay and hematoxylin and eosin staining (H&E). The expression levels of YAP1 and perilipin2 (PLIN2) were detected using Western blot and immunohistochemistry (IHC) in liver tissues. Finally, active ingredients of SNS decoction and SNS serum were identified by liquid chromatography-mass spectrometry (LC-MS). Finally, molecular docking was performed between the compounds in SNS and YAP1 to analyze their active interaction. ResultsCellular experiments showed that SNS serum reduced LD vacuoles and YAP1 expression in OA-induced HepG2 cells. Animal experiments confirmed that LD vacuoles, PLIN2 expression (3.16-fold), and YAP1 expression (2.50-fold) were increased in the HFD group compared with the normal diet (ND) group. SNS reduced LD vacuoles, TG content (0.84-fold), PLIN2 expression (0.33-fold), and YAP1 expression (0.27-fold) compared with the normal saline (NS) group in Yap1Flox mice with MAFLD. In SNS, baicalein-6-glucuronide, desoxylimonin, galangin-7-glucoside, glycyrrhizic-acid, licoricesaponin-K2, and nobiletin showed a high binding effect with YAP1. Knockout of hepatocyte YAP1 reduced LD vacuoles, TG content (0.40-fold), and PLIN2 expression (0.62-fold) in mice. Meanwhile, SNS reduced LD vacuoles, TG content (0.70-fold), and PLIN2 expression (0.19-fold) in Yap1LKO mice with MAFLD. The effect of SNS in reducing TG and PLIN2 was diminished in Yap1LKO mice compared with Yap1Flox mice. ConclusionSNS reduced LD deposition and YAP1 expression in MAFLD liver cells both in vivo and in vitro. YAP1 was highly expressed in livers with MAFLD, and knockout of hepatocellular YAP1 reduced LD deposition in mice. SNS reduced LD deposition associated with decreased YAP1 in MAFLD liver cells.

CcTCM: A quantitative component and compound platform for promoting the research of traditional Chinese medicine

Traditional Chinese medicine (TCM) databases play a vital role in bridging the gap between TCM and modern medicine, as well as in promoting the popularity of TCM. Elucidating the bioactive ingredients of Chinese medicinal materials is key to TCM modernization and new drug discovery. However, one drawback of current TCM databases is the lack of quantitative data on the constituents of Chinese medicinal materials. Herein, we present ccTCM, a web-based platform designed to provide a component and compound-content-based resource on TCM and analysis services for medical experts. In terms of design features, ccTCM combines resource distribution, similarity analysis, and molecular-mechanism analysis to accelerate the discovery of bioactive ingredients in TCM. ccTCM contains 273 Chinese medicinal materials commonly used in clinical settings, covering 29 functional classifications. By searching and comparing, we finally adopted 2043 studies, from which we collected the compounds contained in each TCM with content greater than 0.001 %, and a total of 1449 were extracted. Subsequently, we collected 40,767 compound-target pairs by integrating multiple databases. Taken together, ccTCM is a versatile platform that can be used by TCM scientists to perform scientific and clinical TCM studies based on quantified ingredients of Chinese medicinal materials. ccTCM is freely accessible at http://www.cctcm.org.cn.

Chronic low back pain and its impact on physical function, mental health, and health-related quality of life: a cross-sectional study in Singapore

Chronic low back pain, defined as low back pain lasting more than 3 months, is a globally prevalent health problem with significantly high medical and economic burden on individuals and the society. This study aimed to estimate the prevalence of chronic low back pain and examine its association with health outcomes including physical function, mental health, and quality of life among adult population in Singapore. Cross-sectional secondary data analysis was performed using baseline data of the 1941 adults (mean age: 52.6 years, range: 21–97 years) from a representative population health survey conducted in the Central region of Singapore. Those with self-reported chronic low back pain in past six months were identified. The Late-Life Function and Disability Instrument, Patient Health Questionnaire-9, and EQ-5D-5L were used to measure physical function and limitation, mental health, and health-related quality of life, respectively. Generalized Linear Regressions were used to examine the association of chronic low back pain with physical function, limitation, depressive symptoms, and health-related quality of life. There were 8.1% (n = 180) participants reporting having chronic low back pain in past six months, among whom 80.5% sought treatments at either primary care, specialist outpatient, or Traditional Chinese Medicine clinics. Individuals with chronic low back pain reported poorer physical function, more limitations in performing major life tasks and social activities, more depressive symptoms, and lower health-related quality of life (all p < 0.01), even after adjusting for socio-demographics, lifestyle factors, and number of morbidities. The prevalence of chronic low back pain was 8.1% among the study population. Chronic low back pain was associated with poorer physical function, more limitations and depressive symptoms, and lower health-related quality of life. The findings highlight the significant impact of chronic low back pain on physical function and limitation, mental health, and health-related quality of life in a general population. Increased awareness on prevention, early and proper management of low back pain, and rehabilitation policies are required to better tackle the burden of low back pain at the population level.

A Promising Target of Langchuangding Prescription Treating Systemic Lupus Erythaematosus Integrated Network Pharmacology with HPLC-MS and Molecular Docking.

Systemic lupus erythematosus (SLE) is a chronic multisystem autoimmune disorder affecting almost any organ system without effective treatment. Based on accumulating evidence, activated T cells are key cause promoting the pathogenesis of SLE. A traditional clinic Langchuangding formula (LCD) is an effective clinical traditional Chinese medicine prescription for SLE with few side effects and good patient compliance. However, the mechanism of how LCD affects SLE remains unclear. Targets related to LCD and SLE were predicted and overlapped to construct protein-protein interaction (PPI) for screening core target. Subsequently, flow cytometry analysis and Western-blot method were used to verify the expression levels of target gene in LCD serum treated-Jurkat T cells. The main compounds of LCD were identified by HPLC-MS and further docked with the core targe. 283 protein targets in LCD, 1498 SLE targets and 150 common targets were obtained to construct protein-protein interaction (PPI). Network pharmacology results suggested that LCD was closely related to CASP3 target. To verify the prediction of pharmacological mechanism of LCD treatment for SLE, we investigated the anti-proliferative effects of LCD-treated rat serum on β-oestradiol (300 pg/mL)-activated Jurkat T cells in vitro using a CCK-8 kit and flow cytometry analysis and then analyzed the CASP3 expression levels. Vitro experiments confirmed that LCD serum could suppress the proliferation (p < 0.05) and induce apoptosis of the activated T cells through up-regulating CASP3 expression levels. Interactions between CASP3 target and LCD were further validated integrating HPLC-MS analysis and molecular docking. The results showed that LCD could relieve SLE, which might be attributed to inducing the activated T cells apoptosis by up-regulating CASP3 expression levels. The network pharmacology and molecular docking approach provide a new insight for deepening understanding about TCM. LCD potentially represents a promising therapeutic prescription for SLE supplement treatment with no adverse effects.

A clinical herbal prescription Gu-Shu-Kang capsule exerted beneficial effects on the musculoskeletal system of dexamethasone-treated mice by acting on tissue IGF-1 signalling pathway

Context Gu-Shu-Kang (GSK) is a clinical traditional Chinese medicine prescription for the treatment of primary osteoporosis. Objective This study investigates the protection of GSK against dexamethasone (Dex)-induced disturbance of musculoskeletal system in male mice and to identify the underlying mechanism. Materials and methods Male C57BL/6 mice in Dex-treated groups were orally administered (i.g.) with vehicle, low dose (0.38 g/kg), middle dose (0.76 g/kg), or high dose (1.52 g/kg) of GSK for 8 weeks. A control group was designed without any treatment. The quadriceps femoris, tibialis anterior and gastrocnemius were harvested. Molecular expression was determined by RT-PCR and immunoblotting. Results Treatment with GSK enhanced weight-loaded swimming time (from 411.7 ± 58.4 s in Dex group to 771.4 ± 87.3 s in GSK-M) and grip strength (from 357.8 ± 23.9 g in Dex group to 880.3 ± 47.6 g in GSK-M). GSK produced a rise in cross-sectional area of myofibers and promoted a switching of glycolytic-to-oxidative myofiber. The administration with GSK affected expression of muscle regulatory factors shown by the down-regulation in MuRF-1 and atrogin-1 and the up-regulation in myogenic differentiation factor (MyoD) and myosin heavy chain (MHC). GSK stimulated tissue IGF-1 signalling pathway (IGF-1R/PI3K/Akt), not only in skeletal muscle but also in bone associated with the amelioration of trabecular bone mineral density and the improvement of osteogenesis. Conclusions These findings revealed the potential mechanisms involved in the beneficial effects of Gu-Shu-Kang on musculoskeletal system in mice with challenging to dexamethasone, and this prescription may have applications in management for muscle atrophy and osteoporosis triggered by glucocorticoid.

Validation of the Chinese version of the Somatic Symptom Scale-8 in patients from tertiary hospitals in China.

ObjectiveTo validate the Chinese language version of the Somatic Symptom Scale-8 (SSS-8) in a sample of outpatients attending tertiary hospitals in China.Materials and methodsA Chinese language version of the SSS-8 was completed by outpatients (n = 699) from psychosomatic medicine, gastroenterology/neurology, and traditional Chinese medicine clinics of nine tertiary hospitals between September 2016 and January 2018 to test the reliability. The Patient Health Questionnaire-15 (PHQ-15), the Somatic Symptom Disorder–B Criteria Scale (SSD-12), the Patient Health Questionnaire-9 (PHQ-9), the General Anxiety Disorder-7 (GAD-7) scale, the Medical Outcome Study 12-item Short Form Health Survey (SF-12) and the World Health Organization Disability Assessment Schedule (WHO DAS 2.0) were rated to test construct validity. The criterion validity was tested by using the Semi-structured Clinical Interview for DSM-5 (Research Version) (SCID-5-RV) for somatic symptom disorder (SSD) as the diagnostic gold standard to explore the optimal cutoff score of the SSS-8.ResultsThe average age of the recruited participants was 43.08 (±14.47). 61.4% of them were female. The internal consistency derived from the sample was acceptable (Cronbach α = 0.78). Confirmatory factor analyses resulted in the replication of a three-factor model (cardiopulmonary symptoms, pain symptoms, gastrointestinal and fatigue symptoms) (comparative fit index = 0.95, Tucker-Lewis index = 0.92, root mean square error of approximation = 0.10, 90% confidence interval = 0.08–0.12). The SSS-8 sum score was highly associated with PHQ-15 (r = 0.74, p < 0.001), SSD-12 (r = 0.64, p < 0.001), GAD-7 (r = 0.59, p < 0.001), and PHQ-9 (r = 0.69, p < 0.001). The patients with more severe symptoms showed worse quality of life and disability The optimal cutoff score of SSS-8 was 9 (sensitivity = 0.67, specificity = 0.68).ConclusionOur preliminary assessment suggests that the Chinese language version of the SSS-8 has reliability and validity sufficient to warrant testing further in research and clinical settings.

Green Practices and Innovations of Traditional Chinese Medicine (TCM) Industry in Singapore: Idea Worth Sharing

TCM health benefits and pressure to thrive TCM businesses while taking care of the sustainability of resources has challenged the TCM industry to produce more with less. It is of interest to know how TCM businesses innovate to sustainability through green practices. By capturing the perspectives of TCM organizational stakeholders on practices to minimize the negative impacts on the local environment by TCM enterprises (clinics) in Singapore from the lens of a qualitative exploratory study, the present study explored the presence of green practices and innovations of TCM organizational stakeholders though it is less clear whether these engagements are conducted out of the intention to be green, as these are daily practices at TCM clinics. The phenomenological approach was applied to examine the lived experiences of study participants who work or had worked at TCM clinics in Singapore. The highlights of the paper stressed inadequate focus on green practices at the organizational level to achieve sustainable development targets of TCM industry in Singapore, despite the existence of self-awareness at the individual level to protect the environment. The findings can be building blocks for future research on green and policy making. Green practices and innovations to stay healthy while protecting the environment, with more sensible choices, can bring differences to humans’ lives.

Analysis of the pharmacodynamic difference between Xiaojin Pills taken with Chinese Baijiu and water based on serum pharmacochemistry and pharmacokinetics

Ethnopharmacological relevanceXiaojin Pills (XJPs), which has the function of dissipating knots and dispersing swelling, removing blood stasis, and relieving pain, is a classic prescription for the treatment of mammary glands hyperplasia. It is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinics. Previous studies have shown that the efficacy of XJPs “taken orally after soaked with Chinese Baijiu” in tradition was significantly better than that of taking it orally with water in modern in terms of activating the blood, anti-inflammation, analgesia, anti-mammary gland hyperplasia, anti-breast cancer and its metastasis in vitro and in vivo, especially under low-dose conditions. However, the material basis for the difference in efficacy between XJP&B and XJP&W is still unclear. Aim of the studyTo analyze the material basis of the significant difference in efficacy between XJP&B and XJP&W from the perspective of serum pharmacochemistry and pharmacokinetics, and clarified the scientific connotation of XJPs “taken orally after soaked with Chinese Baijiu”. Materials and methodsUltra-high performance liquid chromatography-mass spectrometry combined with a multivariate statistical analysis method were used to screen the differential components in the Chinese Baijiu extract and the water extract of XJPs and the corresponding residues, so as to clarify the differential components between XJP&B and XJP&W in vitro. The migrating components in the blood after XJP&B and XJP&W were characterized by serum pharmacochemical methods, in order to clarify the differential components in rats. The pharmacokinetic parameters of the representative components absorbed into the blood were compared between XJP&B and XJP&W by the pharmacokinetics study method, in order to determine the dynamic changes of the representative components in rats. ResultsThe identification results of different components in vitro showed that there were 34 and 12 different compounds between the Chinese Baijiu extract and water extract of XJPs, and the residues after Chinese Baijiu extraction and water extraction, respectively. The content of different components such as arachidonic acid, ursolic acid, 3-acetyl-11-keto-β-boswellic acid, 2α-hydroxyursolic acid, and oleanolic acid was higher in the Chinese Baijiu extract, which was more than twice the content in the water extract. The results of the serum pharmacochemistry study indicated that 42 prototype components were identified in the serum of rats after XJP&B and XJP&W, including organic acids, alkaloids, steroids, and terpenoids. And XJP&B increased the absorption of the prototype components of organic acids in XJPs into the blood. The pharmacokinetic study results of representative components demonstrated that the mean plasma concentration-time profile and pharmacokinetic parameters of muscone, aconitine, and 3-acetyl-11-keto-β-boswellic acid were significantly different between XJP&B and XJP&W. Compared with XJP&W, the Cmax and AUC0-t of muscone and aconitine in XJP&B were higher, and the T1/2 and MRT0-t of 3-acetyl-11-keto-β-boswellic acid in XJP&B were relatively longer. ConclusionThis research proved that “taking XJPs orally after being soaked with Chinese Baijiu” can increase the dissolution and absorption of active ingredients in XJPs, increase the plasma concentration and content of representative ingredients, and prolong its action time, thus enhancing the biological activity of XJPs in vitro and in vivo. To a certain extent, this study revealed the material basis of the significantly better efficacy of XJP&B than XJP&W and clarified the scientific connotation of XJPs “taken orally after soaked with Chinese Baijiu”, which can provide a theoretical basis for the optimization of XJPs’ clinical administration method.

Jiangtang Sanhao formula ameliorates skeletal muscle insulin resistance via regulating GLUT4 translocation in diabetic mice.

Jiangtang Sanhao formula (JTSHF), one of the prescriptions for treating the patients with diabetes mellitus (DM) in traditional Chinese medicine clinic, has been demonstrated to effectively ameliorate the clinical symptoms of diabetic patients with overweight or hyperlipidemia. The preliminary studies demonstrated that JTSHF may enhance insulin sensitivity and improve glycolipid metabolism in obese mice. However, the action mechanism of JTSHF on skeletal muscles in diabetic mice remains unclear. To this end, high-fat diet (HFD) and streptozotocin (STZ)-induced diabetic mice were subjected to JTSHF intervention. The results revealed that JTSHF granules could reduce food and water intake, decrease body fat mass, and improve glucose tolerance, lipid metabolism, and insulin sensitivity in the skeletal muscles of diabetic mice. These effects may be linked to the stimulation of GLUT4 expression and translocation via regulating AMPKα/SIRT1/PGC-1α signaling pathway. The results may offer a novel explanation of JTSHF to prevent against diabetes and IR-related metabolic diseases.

Sinisan alleviates depression-like behaviors by regulating mitochondrial function and synaptic plasticity in maternal separation rats

BackgroundSinisan (SNS) consists of four kinds of herbs, which is the core of antidepressant prescription widely used in traditional Chinese medicine clinic treatment for depression induced by early life stress. However, the role and precise mechanism of SNS antidepressant have not yet been elucidated. PurposeThis study aimed to investigate the mechanism SNS on antidepressant of regulating mitochondrial function to improve hippocampal synaptic plasticity. Methods90 Sprague-Dawley (SD) rats male pups on Post-Natal Day (PND) 0 were randomly divided into Control group (ddH20), Model group (ddH20), Fluoxetine group (5.0 mg/kg fluoxetine), and SNS-L group (2.5 g/kg SNS), SNS-M group (5.0 g/kg SNS) and SNS-H group (10.0 g/kg SNS), 15 animals per group. Maternal separation (MS) from PND1 to PND21, drug intervention from PND60 to PND90, and behavior tests including sucrose preference test, open field test and forced swimming test from PND83 to PND90 were performed. Synaptic structure and mitochondrial structure were observed by TEM. The expression levels of PSD-95 and SYN were detected by immunohistochemistry and western blot test, the adenosine triphosphate (ATP) content in the hippocampus was detected by assay kits, and the expression levels of Mfn2, Drp1 and Fis1 protein were detected by western bolt test. ResultsSNS can alleviate depression-like and anxiety-like behaviors in MS rats, improve the damage of synapses and mitochondria, reduce the decrease of ATP in hippocampus, and reverse the expression levels of PSD-95, SYN, Mfn2, Drp1, and Fis1 proteins. ConclusionSNS reduced the risk of early life stress induced depression disorder via regulating mitochondrial function and synaptic plasticity. Targeting mitochondrial may be a novel prospective therapeutic avenue for antidepressant.