Pharmacologically significant constituents collectively responsible for anti-sepsis action of XueBiJing, a Chinese herb-based intravenous formulation.

Sepsis, a life-threatening health issue, lacks effective medicine targeting the septic response. In China, treatment combining the intravenous herbal medicine XueBiJing with conventional procedures reduces the 28-day mortality of critically ill patients by modulating septic response. In this study, we identified the combined active constituents that are responsible for the XueBiJing's anti-sepsis action. Sepsis was induced in rats by cecal ligation and puncture (CLP). The compounds were identified based on their systemic exposure levels and anti-sepsis activities in CLP rats that were given an intravenous bolus dose of XueBiJing. Furthermore, the identified compounds in combination were assessed, by comparing with XueBiJing, for levels of primary therapeutic outcome, pharmacokinetic equivalence, and pharmacokinetic compatibility. We showed that a total of 12 XueBiJing compounds, unchanged or metabolized, circulated with significant systemic exposure in CLP rats that received XueBiJing. Among these compounds, hydroxysafflor yellow A, paeoniflorin, oxypaeoniflorin, albiflorin, senkyunolide I, and tanshinol displayed significant anti-sepsis activities, which involved regulating immune responses, inhibiting excessive inflammation, modulating hemostasis, and improving organ function. A combination of the six compounds, with the same respective doses as in XueBiJing, displayed percentage survival and systemic exposure in CLP rats similar to those by XueBiJing. Both the combination and XueBiJing showed high degrees of pharmacokinetic compatibility regarding interactions among the six active compounds and influences of other circulating XueBiJing compounds. The identification of XueBiJing's pharmacologically significant constituents supports the medicine's anti-sepsis use and provides insights into a polypharmacology-based approach to develop medicines for effective sepsis management.

Occurrence of glycidyl esters in infant formula products on the Canadian market between 2015 and 2019.

Glycidyl fatty acid esters (GEs) are processing contaminants formed during refining steps of vegetable oils. 'In vivo' hydrolysis of GEs releases potentially carcinogenic and genotoxic glycidol (2,3-epoxy-1-propanol). Occurrence of GEs in vegetable oils used for infant formula manufacturing may pose a potential health concern for formula-fed infants. Refined oils are commonly used as the main fat ingredient in formula manufacturing. For this study, different infant formula products (powders, concentrates and ready-to-feed formula products) were purchased and analysed in 2015 (35 samples) and 2019 (33 samples). Seven individual GEs were analysed by LC-MS/MS via direct approach by stable isotope dilution analysis, and total bound glycidol concentrations were calculated. Concentrations of bound glycidol in reconstituted formula reached maxima of 40.3 ng/g in the 2015 samples and 31.5 ng/g in the samples collected in 2019, with respective means of 8.7 ng/g and 6.7 ng/g. The analysed bound glycidol concentrations are comparable with concentration ranges from other studies, but are higher than observed in studies from the European market. Temporal trend data show a reduction of bound glycidol concentrations in 2019. GE concentrations were compared across different manufacturers.

Structurally diverse alkaloids from Buxus sempervirens with cardioprotective activity.

Extensive phytochemical study of the methanol extract of twigs and leaves of Buxus sempervirens resulted in the identification of 17 Buxus alkaloids, including 12 new ones, namely buxusemines A-L (1-12). Their structures were delineated by detailed analysis of the HRESIMS and NMR data, as well as quantum chemical NMR calculations. Buxusemine A (1) represents the second Buxus alkaloid with a unique spiro[4.6]undecatriene moiety, buxusemines B-C (2-3) are a rarely occurring class of Buxus alkaloids featured with an additional five-membered ring through the ether or lactone linkage between C-10 and C-23, and buxusemines D-F (4-6) are another rare type of Buxus alkaloids with an epoxy motif. In the assessment of their bioactivities, buxusemine F (6) and buxanoldine (17) displayed more potent protective effects than the positive control cyclovirobuxinum D in the doxorubicin-induced cardiac injury model.

Hypolipidemic and Hepatoprotective Effects of Polysaccharides Extracted from Liriope spicata Var. Prolifera in C57BL/6J Mice with High-Fat Diet-Induced Hyperlipidemia.

In this study, C57BL/6J mice with high-fat diet- (HFD-) induced hyperlipidemia were treated with total Liriope spicata var. prolifera polysaccharides (TLSP: 200, 400, and 800 mg/kg body weight), simvastatin (3 mg/kg body weight), or saline for 8 weeks, respectively. The results showed that TLSP had strong lipid-lowering and hepatoprotective effects on C57BL/6J mice with HFD-induced hyperlipidemia. TLSP administration significantly reduced serum total cholesterol (TC), triglyceride (TG), and low-density lipoprotein cholesterol (LDL-C) levels and downregulated the expressions of peroxisome proliferator-activated receptor (PPAR)γ and fatty acid synthase (FAS) in the adipose and liver tissues of the mice. TLSP exerted hypolipidemic and hepatoprotective effects by activating lipid/bile acid metabolism via the FXH-SHP/CYP7A1 and SEBP-1c/FAC/ACC signaling pathways. Thus, TLPS is a promising natural polymer with hepatoprotective and hypolipidemic properties.

[Effect of acupuncture and estazolam on episodic memory and sleep structure in patients with chronic insomnia disorder: a randomized controlled trial].

OBJECTIVE: To compare the effect on chronic insomnia disorder (CID) and influences on episodic memory and sleep structure between acupuncture and estazolam tablets. METHODS: A total of 140 CID patients were randomized into a meridian-point group (46 cases, 1 case dropped off), a non-meridian-and-non-acupoint group (47 cases, 2 cases dropped off) and a medication group (47 cases, 2 cases dropped off). In the meridian-point group, Baihui (GV 20), Shenmen (HT 7), Sanyinjiao (SP 6), Zhaohai (KI 6) and Shenmai (BL 62) were selected and the routine acupuncture was applied. In the non-meridian-and-non-acupoint group, the needling technique was same as the meridian-point group. Acupuncture was given once daily for 4 weeks in the above two groups. In the medication group, estazolam tablets were administered orally, taken 1 to 2 mg per night, consecutively for 4 weeks. Before and after treatment, the changes in the following indexes were observed in each group, i.e. the score of insomnia severity index (ISI), the score of auditory verbal memory test (AVMT) and the relevant indexes of sleep structure [total sleep time (TST), sleep onset latency (SOL), wake after sleep onset (WASO), sleep efficiency (SE) and the percentage of non rapid eye movement phase 1, 2 and 3 (N1, N2 and N3) and rapid eye movement time (REM) in TST]. RESULTS: After treatment, ISI scores were reduced in the meridian-point group and the medication group (P<0.01), the score in the meridian-point group was lower than the medication group and the non-meridian-and-non- acupoint group respectively (P<0.01) and that in the medication group was lower than the non-meridian-and-non-acupoint group (P<0.01). After treatment, the score of each of immediate recall, short-term delayed recall, long-term delayed recall and delayed recognition of AVMT was increased in the meridian-point group and the medication group respectively (P<0.01, P<0.05) and the score of each item of AVMT in the meridian-point group was higher than the medication group and the non-meridian-and-non-acupoint group respectively (P<0.01, P<0.05). The scores of immediate memory and delayed recognition in the medication group were higher than the non-meridian-and-non-acupoint group respectively (P<0.01). After treatment, SOL, WASO and N1% were all reduced (P<0.01) and TST, SE, N3% and REM% were all increased (P<0.01, P<0.05) in the meridian-point group and the medication group, N2% in the meridian-point group was reduced (P<0.01). After treatment, N1% and N2% in the meridian-point group were lower than the medication group (P<0.01) and N3% and REM% were higher than the medication group (P<0.01). After treatment, TST, SE and N3% in the meridian-point group and the medication group were all higher than the non-meridian-and-non-acupoint group respectively (P<0.01, P<0.05) and SOL, WASO and N1% were lower than the non-meridian-and-non-acupoint group respectively (P<0.01). REM% in the meridian-point group was also higher than the non-meridion-and-non-acupoint group (P<0.01), and N2% in the meridian-point group was also lower than the non-meridian-and-non-acupoint group (P<0.01). CONCLUSION: Compared with estazolam, acupuncture much better improves sleep quality and episodic memory in patients with chronic insomnia disorder, which is possibly related to the regulation of sleep structure of patients in treatment with acupuncture.

An overview of the safety, clinical application and antiviral research of the COVID-19 therapeutics.

Since a novel coronavirus pneumonia outbreak in late December 2019, coronavirus disease -19 (COVID-19) epidemic has gradually spread worldwide, becoming a major public health event. No specific antivirals are currently available for COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The treatments for COVID-19 are mainly based on the experiences of similar virus such SARS-CoV, MERS-CoV, HIV and influenza viruses. Scientists have taken great efforts to investigate the effective methods for the treatment of COVID-19. Up to now, there are over 1000 clinical studies for COVID-19 all over the world. In this article, we reviewed the current options for COVID-19 therapy including small molecules such as Remdesivir, Favipiravir, Lopinavir/Ritonavir etc, peptide inhibitors of ACE2, Traditional Chinese Medicines and Biologics such as SARS-CoV-2-specific neutralizing antibodies, mesenchymal stem cells and vaccines etc. Meanwhile, we systematically reviewed their clinical safety, clinical applications and progress of antiviral researches. The therapeutic effect of these antiviral drugs is summarized and compared, hoping to provide some ideas for clinical options of COVID-19 treatment and also provide experiences for the life-threatening virus diseases in the future.

The hepatoprotective effects of XCHD and MgIG against methotrexate-induced liver injury and inflammation in rats through suppressing the activation of AIM2 inflammasomes.

BACKGROUND: Recent studies have shown that drug-induced liver injury may be related to the immune response activated by drugs. A cytosolic dsDNA inflammasome called absent in melanoma 2 (AIM2) was found to be associated with aseptic inflammation. The present study aimed to explore the effects of on the liver injury and inflammation in methotrexate (Mtx)-induced rats. METHODS: Sprague Dawley (SD) rats were selected and classified into 4 groups randomly, includes control group, Mtx group, Mtx-Xiaochaihu decoction (XCHD) group and Mtx-magnesium isoglycyrrhizinate (MgIG) group. Light microscopy was used to examine histological specimens after hematoxylin-eosin (HE) staining. The AST levels in liver tissue and blood serum ALT in the rats were assessed with enzyme linked immunosorbent assay (ELISA). Then AIM2 expression and inflammatory factors, including caspase-1, IL-18, and IL-1ß, in the liver biopsy specimens of rats were detected by immunohistochemistry. Furthermore, the correlation between inflammatory and AIM2 expression factors was comprehensively analyzed. RESULTS: Functional and structural hepatotoxicity can be caused by the exposure to Mtx, which was supported by the improved biochemical marker levels and the worse histopathological changes in liver tissue. Compared with the Mtx group, the levels of liver enzymes ALT and AST, histological deterioration in the liver tissues were effectively decreased by XCHD and MgIG treatment, respectively. In addition, the expression of AIM2, caspase-1 and IL-1ß was observably higher in the Mtx group, which was apparently inhibited in the Mtx-XCHD and Mtx-MgIG groups. There was no obvious change in IL-18 expression among four groups. AIM2 expression were positively associated with the severity of liver inflammation and had a higher relevance with caspase-1 expression. CONCLUSIONS: AIM2 inflammasome in hepatocytes has a significant effect on the development of Mtx-induced liver injury, which can be ameliorated by both XCHD and MgIG treatment. The latent mechanism and potential signal pathway require further study.

Characterization of the complete chloroplast genome of Bletilla striata (Orchidaceae: Bletilla), the herb in China.

Chloroplast (cp) genome sequences have been become a useful tool for phylogenetic and evolutionary studies in the herb. In this study, the complete cp genome of Bletilla striata was assembled. The complete cp genome is circular of 157,016 base pairs (bp) in length, which harbours a large single-copy region (85,821 bp), a small single-copy region (17,743 bp), and two inverted-repeat regions (each one of 26,726 bp). The cp genome of B. striata contains 139 genes, including 94 protein-coding genes (PCGs), 37 transfer RNA (tRNAs), and 8 ribosome RNA (rRNAs). The overall nucleotide content of the cp genome is A of 31.0%, T of 31.8%, C of 18.9%, and G of 18.3%, with a total AT content of 62.8% and GC content of 37.2%. However, the phylogenetic relationship analysis using maximum-likelihood (ML) method, which the result showed that the position of B. striata was situated as Bletilla ochracea in Orchidaceae. This study will be helpful for studies on the cp genetic engineering and medicinal herb value of Orchidaceae species in further.

Development and validation of the Chinese Version of Spiritual Interests Related Illness Tool for patients with cancer in Taiwan.

PURPOSE: The purpose of the study was to develop and validate the Chinese Version of Spiritual Interests Related Illness Tool (C-SpIRIT) for patients with cancer in Taiwan. METHODS: Translation, adaptation, and content validation were performed based on the 44-item Spiritual Interests Related Illness Tool. The psychometric validation was conducted based on 260 participants who were recruited from the oncology outpatient clinic of a medical center in southern Taiwan. The data were analyzed using exploratory factor analysis, Cronbach's alpha, and Pearson's correlations. RESULTS: Five subscales (related to beliefs/religion, positive attitudes toward life, love to/from others, seeking for the meaning of life, and peaceful mind) were extracted from an exploratory factor analysis. The five subscales (with 21 items) accounted for 50.43% of the variance. The evidence based on concurrent validity was supported by a significant correlation (r = 0.95) between the 33-itm C-SpIRIT and the 21-item C-SpIRIT. Cronbach's α values (0.73-0.88) demonstrated internal item consistency of the C-SpIRIT. CONCLUSIONS: This preliminary 21-item and 5-factor constructed C-SpIRIT demonstrated a valid and reliable instrument to assess the spiritual needs of patients with cancer in Taiwan. In addition, it is a handy tool for oncology nursing practitioners to gage their patients' spiritual needs.

Beneficial effect of lycopene on anti-diabetic nephropathy through diminishing inflammatory response and oxidative stress.

Lycopene is widely used for nutritional supplementation, but the potential benefits in diabetic nephropathy (DN) remains unknown. This study aimed to highlight the therapeutic prospect of lycopene against streptozotocin (STZ)-induced kidney injury in mice. During the process of the experiments, biochemical kits were employed to determine the diabetes-metabolic parameters in STZ-lesioned mice. Routine pathological and ultrastructural observations were screened for the histological changes of kidney tissue. Moreover, immunohistochemical staining was used to investigate the inflammatory conditions expressed in kidney tissue. Furthermore, intrarenal heme oxygenase 1 (HO-1) mRNA level was assayed via RT-PCR and Western blot analyses. The results showed that lycopene alleviated the lesioned signs of DN mice induced by STZ, accompanied with the increase in body weight, reduced serum concentrations of blood sugar and low-density lipoprotein cholesterol (LDL-C), elevated high-density lipoprotein cholesterol (HDL-C) level, and the decrease in urine protein content. In addition, oxidative defense patterns in the kidneys of DN mice were ameliorated, as shown in augmented bioactivities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and in turn lowered malondialdehyde (MDA) content. The immunohistochemical experiment exhibited that lycopene intake contributed to attenuation of nuclear factor-kappa B (NF-κB) and tumor necrosis factor alpha (TNF-α) expressions in kidney tissue. Moreover, intrarenal HO-1 level was up-regulated in the presence of lycopene. Our findings provide the evidence that lycopene protects kidney cells from STZ-induced lesions via inhibiting NF-κB signal pathway for anti-inflammation and attenuating oxidative stress for anti-dysmetabolism.

Antidiabetic Activity of Polysaccharides from Tuberous Root of Liriope spicata var. prolifera in KKAy Mice.

Tuberous root of Liriope spicata var. prolifera has been widely used as a traditional Chinese medicine for the treatment of diabetes. The present study investigated the antidiabetic effect and the potential mechanisms of two new polysaccharides (LSP1, LSP2) and the total polysaccharides (TLSP), isolated from the tuberous roots. Upon the intragastric administration in obese insulin-resistant diabetic KKAy mice for 28 days, TLSP, LSP1, and LSP2 all caused a remarkable decrease of fasting blood glucose and significant improvement of insulin resistance and serum lipid metabolism in diabetic mice. In addition, liver histological analysis showed that TLSP, LSP1, and LSP2 significantly ameliorated the hepatocyte hypertrophy and decreased the lipid accumulation in the mice liver. Further experiments suggested that TLSP, LSP1, and LSP2 effectively inhibited hepatic gluconeogenesis and increased hepatic glycolysis and hepatic glycogen content. Furthermore, the mechanistic analysis showed the increased expression of insulin-receptor α subunit, insulin-receptor substrate-1, phosphatidylinositol 3-kinase, and peroxisome proliferators-activated receptors γ . These results suggested that TLSP, LSP1, and LSP2 manifest strong antidiabetic activity, therefore hold a great promise for therapeutic application in diabetic therapy and other related metabolic disorders.

Hypoglycemic polysaccharides from the tuberous root of Liriope spicata.

Previous studies showed that the water extract and crude polysaccharides from the tuberous root of Liriope spicata var. prolifera showed high hypoglycemic and hypolipidemic activities. In the present study, two new water-soluble polysaccharides, named LSP1 and LSP2, were isolated from the active crude polysaccharides by DEAE-cellulose 52 and AB-8 macroporous resin chromatography and tested for their hypoglycemic effects. On the basis of the chemical and physical data obtained, LSP1 and LSP2 are two fructans with the molecular weights 3.20 and 4.29 kDa, respectively, which both have a backbone structure of beta-(1-->2)-fructosyl residues that branches at O-6 with fructosyl residues and terminates with a glucosyl residue and a fructosyl residue. Preliminary activity tests revealed that both LSP1 and LSP2 caused a significant decrease of the fasting blood glucose (FBG) and a significant improvement on glucose tolerance in type 2 diabetic mice. These results suggest that LSP1 and LSP2 show high potential to be explored as natural oral hypoglycemic agents.

Effects of water extract and crude polysaccharides from Liriope spicata var. prolifera on InsR/IRS-1/PI3K pathway and glucose metabolism in mice.

AIM OF THE STUDY: The present study was designed to investigate the effects of water extract (WE) and crude polysaccharides (CPs) from the tuberous root of Liriope spicata var. prolifer on the InsR/IRS-1/PI3K pathway and glucose metabolism in type 2 diabetic mice. MATERIALS AND METHODS: WE and CPs were administered orally at different doses (200 and 100mg/kg body weight) to streptozotocin (STZ)-induced type 2 diabetic male BABL/c mice, respectively. After 4 weeks of administration, immunohistochemistry and western blot were applied to detect the expression levels of insulin receptor-alpha (InsR-alpha), insulin receptor substrate-1 (IRS-1) and phosphatidylinositol 3-kinase (PI3K) in renal tissues of mice. Moreover, the hepatic glycogen content, glucokinase (GK) and glucose-6-phosphatase (G6Pase) activities were measured to investigate the effect of WE and CPs on glucose metabolism. RESULTS: Compared with diabetic control, greater immunostaining for InsR-alpha, IRS-1 and PI3K was present in the tubulointerstitial regions of WE and CPS groups in renal tissues and the expression levels of these three signal molecules from WE and CPs groups were significantly increased; the glycogen content and GK activity from WE and CPs groups in liver were significantly increased, yet the G6Pase activity was significantly lower. CONCLUSIONS: It is demonstrated that WE and CPs can ameliorate insulin signaling transduction and glucose metabolism, as a result, lessen IR and hyperglycemia eventually. So, this study has provided more powerful evidences for Liriope spicata var. prolifer to be a potential hypoglycemic agent and insulin sensitizer.

Influence of TCM therapy for supplementing Pi and nourishing Shen on dendritic cell function in patients with chronic hepatitis B treated by lamivudine.

OBJECTIVE: To observe the influence of traditional Chinese medicine (TCM) therapy for supplementing Pi () and nourishing Shen (, SPNS) on dendritic cell function in patients with chronic hepatitis B (CHB) treated by lamivudine. METHODS: Sixty CHB patients with positive HBeAg were equally randomized by digital table into two groups: the observation group and the control group. Patients in the control group were treated with lamivudine only, while patients in the observation group were treated with lamivudine combined with SPNS fomula, for 12 weeks. The phenotype and function of dendritic cell, as well as its secretion factor interleukin 12 (IL-12) in all patients were determined after termination of therapy and the impacts on alanine transaminase (ALT) and HBVDNA were observed. RESULTS: The phenotypes of dendritic cells such as CD1a, CD80, CD86, human leukocyte antigen (HLA-DR) and intercellular adhesion molecule-1, as well as the levels of stimulation index (SI) and IL-12 were higher in the observation group than those in the control group (P<0.05 or P<0.01). Meanwhile, signififi cant difference between the two groups was also shown in the normalizing rates of ALT and HBV-DNA (P<0.05). CONCLUSION: TCM therapy for SPNS can signifificantly improve the function of dendritic cells in patients with CHB treated by lamivudine and enhance the early stage response of patients to the treatment.

Anti-diabetic effects of water extract and crude polysaccharides from tuberous root of Liriope spicata var. prolifera in mice.

AIM OF THE STUDY: The present study was designed to investigate the hypoglycemic and hypolipidemic effects of the water extract (WE) and crude polysaccharides (CPs) obtained from the tuberous root of Liriope spicata (Thund.) var. prolifera Y. T. Ma, which is widely used in prescriptions of traditional Chinese medicine for the treatment of diabetes mellitus. MATERIALS AND METHODS: WE and CPs were administered orally at different doses (200 and 100 mg/kg body weight) to normal and streptozotocin (STZ)-induced type 2 diabetic male BABL/c mice, respectively. The fasting blood glucose (FBG), lipids and insulin in serum were estimated and an oral glucose tolerance test (OGTT) was performed for the evaluation of hypoglycemic and hypolipidemic effects. RESULTS: Both doses of WE and CPs did not show any appreciable effect on FBG in normal mice. However, they caused a marked decrease of FBG and a significant improvement on glucose tolerance and insulin resistance in STZ-induced type 2 diabetic mice. In addition, while lowering total cholesterol (TC), triglyceride (TG) and low-density lipoprotein (LDL) cholesterol levels, WE and CPs elevated the relative high density lipoprotein (HDL) cholesterol level (HDL/TC) in serum. Compared to WE, the hypoglycemic and hypolipidemic effects of CPs were more marked. CONCLUSIONS: The results suggest that WE and CPs may have hypoglycemic and hypolipidemic potential for the type 2 diabetes and support the traditional use of the tuberous root of Liriope spicata var. prolifera as a hypoglycemic agent.

[Studies on genetic diversity in cultivated populations of Atractylodes macrocephala].

OBJECTIVE: To investigate the genetic diversity of main germplasm of Atractylodes macrocephala in China and the genetic differentiation of the germplasm of A. macrocephala. METHOD: A molecular marker ISSR was used to analyze the genetic diversity of 7 populations of A. macrocephala and a population of A. lancea. RESULT: Twelve primers were used in the PCR amplification of 86 samples of A. macrocephala and 5 samples of A. lancea. Sixty-three bands with sizes ranged from 100 to 2500 bp were generated from 12 primers. Of all the 63 bands, 55 bands were polymorphic among 86 individuals of A. macrocephala, the percentage of polymorphic bands were 87.30% at the species level. The percentage of polymorphic bands (PPL) for a single population ranged from 58.73% to 71.43% (mean, 64.85%). Among the 7 populations, a population from Panan, GM exhibited highest variability (PPL =71.43%; HE = 0.2835; I = 0.4267). A dendrogram constructed by an unweighted pair group method of cluster analysis showed that populations from Panan constructed one branch and separated from other populations. In the AMOVA analysis, low level of genetic differentiation among populations was detected, 90.52% of the variability existed in population. CONCLUSION: The genetic diversity of cultivated A. macrocephala in China is high, which is good for the production of high quality herb medicine.