Matrine Enhances the Antitumor Efficacy of Chidamide in CTCL by Promoting Apoptosis.

BACKGROUND: Cutaneous T-cell Lymphoma (CTCL) is a rare group of non-Hodgkin lymphoma originating from the skin, which is characterized by T-cell lymphoproliferative disorders. Chidamide, a Chinese original antineoplastic agent with independent intellectual property rights, and matrine, an extract of Chinese herbal medicine, both have been reported to exert effects on the treatment of tumors individually. However, chidamide combined with matrine has not been tested for the treatment of CTCL. METHODS: Both HH and Hut78 CTCL cell lines were treated with chidamide (0.4 µmol/L), matrine (0.6 g/L), or chidamide combined with matrine for 24, 48, and 72 h. Cell viability was estimated by MTS assay at each time point. Flow cytometry was then conducted to detect cell apoptosis. The exact mechanism of chidamide combined with matrine on CTCL cells was detected by Western blotting and further validated in xenograft models of NOD/SCID mice. RESULTS AND DISCUSSION: Compared to the single drug, chidamide combined with matrine showed a more significant effect on proliferation inhibition and apoptosis induction on CTCL cells both in vitro and in vivo. The results from the in vitro and in vivo studies suggested that matrine could enhance the anti-tumor effect of chidamide by increasing the protein expression of cleaved caspase- 3 and decreasing the expression of E-cadherin, NF-κB, p-Bad, and Bcl-2 to activate apoptosis. CONCLUSION: Our data have demonstrated chidamide combined with matrine to exhibit elevated antitumor activity in both CTCL cells and xenograft models of NOD/SCID mice, which may be a potential treatment option for CTCL.

Five new secondary metabolites from Aster tataricus.

Aster tataricus L.f. is highly valued for its rich reserves of bioactive compounds. Our research focused on the identification of previously unreported compounds found within the ethanol extract of A. tataricus. Through meticulous spectroscopic analyses and computational methods like NMR calculations and ECD, we successfully elucidated the structures of five novel compounds termed tatarisides A-E (1-5), alongside two known compounds (6, 7). The anti-inflammatory assays conducted yielded noteworthy results, particularly in relation to compounds 1 and 5. These compounds exhibited significant potential in inhibiting the release of NO in LPS-induced RAW 264.7 cells, as evidenced by their respective IC50 values of 17.81 ± 1.25 µM and 13.32 ± 0.84 µM. The discovery of these new compounds adds to the existing knowledge of A. tataricus's chemical composition and potential applications.

Chemical constituents from Acorus calamus with potent anti-diabetic and hepatoprotective activities.

Three previously undescribed compounds, (+)-7S,8S-syringoylglycerol-7-O-3',4'-dihydroxylphenylethanol (1), (+)-2S,3R-piscidic acid 1-methyl-5-ethyl ester (2), and 2'S-2-acetyl-3-(2,3-dihydroxypropoxyl)furan (3), together with one new natural product, 7S,8S-4,7,8-trihydroxyl-methyl phenylpropionate (4) and a known lignan (7S,8R)-methyl-4',7-epoxy-3,3'-dimethoxy-4,9-dihydroxylignan-9'-oate (5), were isolated from the ethanol extract of Acorus calamus Linn. rhizomes. Their structures were determined based on extensive spectroscopic analyses and computational methods. All the isolated compounds were evaluated for their in vitro GK activating and hepatoprotective activities, and compound 5 exhibited significant GK activating activity at 10-5 mol/L, compound 3 exhibited moderate protective effects to APAP-induced injuries of HepG2 cells at 10-5 mol/L. Furthermore, molecular docking of compound 5 bound with GK was carried out to investigate the possible structural insights into the potential binding patterns.

Amelioration effects of α-viniferin on hyperuricemia and hyperuricemia-induced kidney injury in mice.

BACKGROUND: α-Viniferin, the major constituent of the roots of Caragana sinica (Buc'hoz) Rehder with a trimeric resveratrol oligostilbenoid skeleton, was demonstrated to possess a strong inhibitory effect on xanthine oxidase in vitro, suggesting it to be a potential anti-hyperuricemia agent. However, the in vivo anti-hyperuricemia effect and its underlying mechanism were still unknown. PURPOSE: The current study aimed to evaluate the anti-hyperuricemia effect of α-viniferin in a mouse model and to assess its safety profile with emphasis on its protective effect on hyperuricemia-induced renal injury. METHODS: The effects were assessed in a potassium oxonate (PO)- and hypoxanthine (HX)-induced hyperuricemia mice model by analyzing the levels of serum uric acid (SUA), urine uric acid (UUA), serum creatinine (SCRE), serum urea nitrogen (SBUN), and histological changes. Western blotting and transcriptomic analysis were used to identify the genes, proteins, and signaling pathways involved. RESULTS: α-Viniferin treatment significantly reduced SUA levels and markedly mitigated hyperuricemia-induced kidney injury in the hyperuricemia mice. Besides, α-viniferin did not show any obvious toxicity in mice. Research into the mechanism of action of α-viniferin revealed that it not only inhibited uric acid formation by acting as an XOD inhibitor, but also reduced uric acid absorption by acting as a GLUT9 and URAT1 dual inhibitor as well as promoted uric acid excretion by acting as a ABCG2 and OAT1 dual activator. Then, 54 differentially expressed (log2 FPKM ≥ 1.5, p ≤ 0.01) genes (DEGs) repressed by the treatment of α-viniferin in the hyperuricemia mice were identified in the kidney. Finally, gene annotation results revealed that downregulation of S100A9 in the IL-17 pathway, of CCR5 and PIK3R5 in the chemokine signaling pathway, and of TLR2, ITGA4, and PIK3R5 in the PI3K-AKT signaling pathway were involved in the protective effect of α-viniferin on the hyperuricemia-induced renal injury. CONCLUSIONS: α-Viniferin inhibited the production of uric acid through down-regulation of XOD in hyperuricemia mice. Besides, it also down-regulated the expressions of URAT1 and GLUT9 and up-regulated the expressions of ABCG2 and OAT1 to promote the excretion of uric acid. α-Viniferin could prevent hyperuricemia mice from renal damage by regulating the IL-17, chemokine, and PI3K-AKT signaling pathways. Collectively, α-viniferin was a promising antihyperuricemia agent with desirable safety profile. This is the first report of α-viniferin as an antihyperuricemia agent.

Effects of L-carnitine Administration on Sperm and Sex Hormone Levels in a Male Wistar Rat Reproductive System Injury Model in a High-Altitude Hypobaric Hypoxic Environment.

The plateau environment impacts male reproductive function, causing decreased sperm quality and testosterone levels. L-carnitine can improve the semen microenvironment. However, the role of L-carnitine in a high-altitude environment remains unclear. In our study, we investigated the effects of L-carnitine administration in a male Wistar rat reproductive system injury model in the context of a simulated high-altitude environment. Rats were randomly divided into a normal control group (group A1, A2-low dose and A3-high dose) and high-altitude model groups (group B, C-low dose and D-high dose) with 20 rats in each group. With the exception of the normal control group exposed to normoxic conditions, the other groups were maintained in a hypobaric oxygen chamber that simulated an altitude of 6000 m for 28 days. In the experimental period, the low-dose groups (A2 and C) were administered 50 mg/kg L-carnitine via intraperitoneal injection once a day, and the high-dose groups (A3 and D) were given 100 mg/kg. After the feeding period, blood samples were collected to assess blood gas, serum hormone levels and oxidative stress. Sperm from the epididymis were collected to analyse various sperm parameters. After obtaining the testicular tissue, the morphological and pathological changes were observed under a light microscope and transmission electron microscopy (TEM). The impact of the simulated high-altitude environment on the rat testis tissue is obvious. Specifically, a decreased testicular organ index and altered indices of arterial blood gas and serum sex hormone levels caused testicular tissue morphological damage, reduced sperm quality, increased sperm deformity rate and altered malondialdehyde (MDA), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) concentrations. The results demonstrate that L-carnitine can be administered as a preventive intervention to reduce the reproductive damage caused by high-altitude hypobaric and hypoxic environments and improve semen quality in a rat model.

Astragaloside IV alleviates stroke-triggered early brain injury by modulating neuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway

Purpose: Stroke is an acute cerebrovascular disease. Astragaloside IV (AS-IV) is an active ingredient extracted from Astragalus membranaceus with an established therapeutic effect on central nervous system diseases. This study examined the neuroprotective properties and possible mechanisms of AS-IV in stroke-triggered early brain injury (EBI) in a rat transient middle cerebral artery occlusion (MCAO) model. Methods: The neurological scores and brain water content were analyzed. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was utilized to determine the infarct volume, neuroinflammatory cytokine levels, and ferroptosis-related genes and proteins, and neuronal damage and molecular mechanisms were evaluated by terminal deoxynucleotidyl transferase dutp nickend labeling (TUNEL) staining, western blotting, and real-time polymerase chain reaction. Results: AS-IV administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-α, interleukin-1ß (IL-1ß), IL-6, and NF-κB, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke. Conclusion: Hence, the findings of this research illustrate that AS-IV administration can improve delayed ischemic neurological deficits and decrease neuronal death by modulating nuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.

Effectiveness and Safety of Early Short-Course, Moderate- to High-Dose Glucocorticoids for the Treatment of Stevens-Johnson Syndrome/Toxic Epidermal Necrolysis: A Retrospective Study.

Objective: To summarise the clinical characteristics of patients with Stevens-Johnson syndrome/toxic epidermal necrolysis syndrome (SJS/TEN) and analyse the efficacy and safety of systemic glucocorticoid therapy. Methods: This study was a retrospective study of 56 patients with SJS/TEN who had been systematically treated with glucocorticoids in the dermatology ward of Peking University Third Hospital from 2010 to 2020. The clinical characteristics, treatment regimen, effects on underlying diseases, incidence and outcome of hormone-related adverse reactions and skin lesion prognosis were summarised and analysed for each patient. Results: ① The allergenic drugs were found to be antibiotics (31.51%), antipyretic and analgesics (21.92%), traditional Chinese medicines and health products (15.07%) and neuropsychiatric drugs (13.70%). ② Based on the 56 patients' scores of toxic epidermal necrosis at admission, the actual mortality rate was 1.8% (1/56), which was significantly lower than the average expected mortality rate of 15.0% (P = 0.032; standardised mortality ratio = 0.13; 95% confidence interval: 0.00-0.53). ③ A total of 33 patients (58.9%) had underlying diseases, of which 10 patients (30.3%) had underlying diseases that fluctuated during treatment but stabilised after symptomatic treatment. ④ During treatment, 73.2% (41/56) of patients had complications that may have been related to systemic glucocorticoids; 97.6% (40/41) had mild symptoms, and 92.7% (38/41) had improved/recovered complications at the time of discharge. Conclusion: ① Antibiotics are still the most common sensitising drugs, and traditional Chinese medicine and health products are also common sensitising drugs. ② Early systemic application of medium- to high-dose glucocorticoids is effective in the treatment of SJS/TEN, and it is beneficial in reducing mortality. ③ The short-term application of medium- to high-dose hormone therapy for SJS/TEN has little effect on underlying diseases. The related complications are mostly mild, and the treatment is safe.

Effects of dietary supplement with a Chinese herbal mixture on growth performance, antioxidant capacity, and gut microbiota in weaned pigs.

Weaning stress decreases the growth performance of piglets and is one of the main concerns of pig industries. Traditional Chinese herbal medicines have been used to reduce the adverse effects of weaning stress as both nutritional supplements and antibiotic substitutes. This study aimed to evaluate the effects of a Chinese herbal mixture (Kangtaile, which contained Paeonia lactiflora, licorice, dandelion, and tea polyphenols) on the growth performances, immune response, antioxidant capacity, and intestinal microbiota of weaned pigs. A total of 400 weaned pigs [Duroc × (Landrace × Yorkshire)] were randomly allocated into one of four treatments: the CON group, fed with basic diet; the HM1 group, fed with basal diet supplemented with 0.5 g herbal mixture/kg diet; the HM2 group, fed with basal diet supplemented with 1.0 g herbal mixture/kg diet; or the HM3 group, fed with basal diet supplemented with 1.5 g herbal mixture/kg diet. The results revealed that dietary supplementation with the herbal mixture for 28 days improved average daily gain and feed conversion ratio, while decreased the diarrhea rate of weaned pigs. Moreover, dietary supple-mentation with the herbal mixture improved the antioxidant capacity through increasing the activity of catalase (CAT) and the total antioxidant capacity (T-AOC) level, while decreasing the concentration of malondialdehyde (MDA) in the serum. Pigs supplemented with herbal mixture presented an increased serum immunoglobulin (Ig)M level on day 14 compared with control pigs. The herbal mixture altered the composition of intestinal microbiota by influencing the relative abundances of Firmicutes and Bacteroidetes at the phylum level. The relative abundances of the Firmicutes and Bacteroidetes were significantly related to the body weight gain of pigs. In conclusion, supplementation of herbal mixture to the diet improved growth performance, immunity, and antioxidant capacity and modified the composition of intestinal microbiota in weaning pigs. This study provided new insights into the nutritional regulation effects of the herbal mixtures on weaned pigs.

Corydecumine G inhibits microglia activation via MAPK pathway in a rat model of neuropathic pain.

BACKGROUND AND PURPOSE: Microglial activation plays an important role in the onset and progression of neuropathic pain by producing a variety of pro-inflammatory cytokines that interact with neurons to enhance neuronal hyperexcitability. Corydalis decumbens (Thunb.) pers., a traditional Chinese medicine has been used to treat mild cancer pain, dementia and to remit cerebral ischemia in clinics. Phenylphthalide isoquinolines are the major type of metabolites of C. decumbens and one of the derivatives, Corydecumine G (Cor G) has been shown to inhibit neuronal excitability. The present study aims to investigate the analgesic efficacy of Cor G in neuropathic pain rat model, the effects of Cor G on microglia activation and the possible mechanisms. EXPERIMENTAL APPROACH: Neuropathic pain was modeled using chronic constriction sciatic nerve injury (CCI) in rats. Western blot, immunofluorescence, and qRT-PCR were used to evaluate the levels of protein and mRNA. KEY RESULTS: Intraperitoneal administration of Cor G concentration-dependently ameliorates mechanical and thermo allodynia, suppresses CCI-induced p38/ERK phosphorylation and spinal cord microglia activation, and attenuates the expression levels of NO, inos, Tnf-α, Pge2 in dorsal horn of L4-L6 spinal cord on the ligation side in CCI rats. Pretreatment with 30 µM Cor G decreased LPS-induced BV2 microglia activation, which occurred via the inos, Tnf-α, Il-1ß, Il-6 and phospho-p38/ERK pathways. CONCLUSIONS AND IMPLICATIONS: Taken together, we suggest that Cor G, the specific phthalide isoquinoline from traditional Chinese medicine Corydalis Decumbentis Rhizoma, may be promising for treatment of neuropathic pain.

Value of serum miR-21, HE4 and CA125 in surveillance for postoperative recurrent or metastatic ovarian cancer.

Objectives: To study the value of serum miR21, human epididymal secretory protein 4 (HE4) and carbohydrate antigen 125 (CA125) in the surveillance for postoperative recurrent or metastatic ovarian cancer. Methods: A total of 169 patients diagnosed with ovarian conditions in Luanzhou Hospital of Traditional Chinese Medicine during January 2016 and March 2019 were divided into a benign lesion (BL) group and an ovarian cancer (OC) group by pathological findings and assigned to a good prognosis (GP) group and a poor prognosis (PP) group according to the follow-up results. A real-time fluorescence quantitative PCR (RT-fqPCR) system was utilized to detect the serum level of miR-21; an enzyme-linked immunosorbent assay (ELISA) was conducted to determine the serum level of HE4; electrochemiluminescence (ECL)-based imaging analysis was performed to measure serum CA125. A receiver operating characteristic (ROC) curve was depicted to analyze the predictive value of serum miR-21, HE4, and CA125 for poor postoperative prognosis in patients with ovarian cancer. Results: Compared with the control group, the BL and OC groups had substantially elevated expression of miR-21, HE4, and CA125 in serum, and the serum levels of miR-21, HE4, and CA125 in the OC group were significantly higher than in the BL group. In the OC group, the serum levels of miR-21, HE4, and CA125 were independent of age and pathological patterns and associated with the clinical staging, degree of transformation and lymphatic metastasis of ovarian cancer; after laparoscopic ovarian tumorectomy, the serum levels of miR-21, HE4, and CA125 were markedly reduced in comparison with the preoperative levels. Compared with the GP group, the PP group experienced a dramatic increase in serum miR-21, HE4, and CA125 expression. The ROC curve showed that the detection of miR-21, HE4, and CA125 was a highly sensitive and specific method to predict the poor prognosis in ovarian cancer; a patient with ovarian cancer was at high risk of a poor prognosis when the serum levels of miR-21, HE4, and CA125 exceeded 1.536, 157.004 pmol/L and 175.243 kU/L, respectively, in which case early intervention should be made to prevent recurrent or metastatic ovarian cancer. Conclusion: Elevated expression of miR-21, HE4, and CA125 in serum is closely associated with the disease status of ovarian cancer. Therefore, the simultaneous detection of these tumor markers has some diagnostic value for postoperative recurrence and metastasis of ovarian cancer.

Clinical study on effect of wrist-ankle acupuncture on incidence of hypertension after intubation during induction of general anesthesia.

OBJECTIVE: To observe the effect of wrist-ankle acupuncture on the incidence of hypertension after tracheal intubation during induction of general anesthesia. METHODS: 200 patients receiving selective surgery under tracheal intubation and general anesthesia in our Hospital were selected and divided into control group and wrist-ankle acupuncture group using the random number table method, with 100 patients in each group. Sufentanil, cisatracurium besilate, remifentanil, etomidate and lidocaine hydrochloride were used for anesthesia induction, and intravenously injected according to the onset time of drugs, successively. The wrist-ankle acupuncture group was needled in bilateral upper 1, 2 and 3 areas, while the control group was treated with false acupuncture.Blood pressure and related blood biochemical indexes were measured and observed at different stages in each group. RESULT: The incidence of blood pressure exceeding 20% and 30% of basal blood pressure within 5 minutes after intubation was as follows:wrist-ankle acupuncture group 11.83% and 6.45%; control group 29.79% and 22.34%, The incidence in the study group was lower than that in the control group. Norepinephrine concentration in the wrist-ankle acupuncture group was significantly lower than that before induction (P < .05), and plasma Norepinephrine concentration in the wrist-ankle acupuncture group was significantly lower than that in the control group after intubation (P < .05). The plasma Norepinephrine concentration in the wrist-ankle acupuncture group was significantly lower than that in the control group after intubation (P < .05). CONCLUSION: wrist-ankle acupuncture can prevent hypertension after intubation during anesthesia induction. Moreover, it is safe, effective, minimally invasive. Therefore, it is easy to be popularized in clinical practice.

Phytochemical Characterizations of Maranthes polyandra (Benth.) Prance.

Two new ursane-type triterpenoids, named Polyanside A (1) and B (2), along with eleven known compounds (3-13), were isolated and elucidated from Maranthes polyandra (Benth.) Prance. The structures of these compounds were elucidated based on chemical evidence and multiple spectroscopic data. Isolated compounds were evaluated for anti-cancer, anti-inflammatory activities, and cytotoxicity on a normal human cell line (BJ). None of them showed activity and cytotoxicity. The hexane fraction was analyzed by GC-MS, resulting in the identification of forty-one compounds. This is the first comprehensive study on the phytochemistry of M. polyandra.

Hypeisoxazole A, a Racemic Pair of Tetrahydroisoxazole-Fused Benzylisoquinoline Alkaloids from Hypecoum erectum and Structural Revision of Hypecoleptopine.

(±)-Hypeisoxazole A (1), a racemic pair of rearranged benzylisoquinoline alkaloids possessing an unprecedented diindeno[2,1-c:2',1'-d] isoxazole scaffold, was isolated from the medicinal herb Hypecoum erectum, along with hypecoleptopine (2), whose structure is now revised as a novel spiro-benzylisoquinoline alkaloid with a 6/6/5/6/6 skeleton. Their structures were determined by comprehensive spectroscopic and spectrometric analyses, X-ray diffraction, and computational studies. Racemic mixture of 2 and its pure enantiomers modulated neuronal excitability activity.

Hypothalamus-habenula potentiation encodes chronic stress experience and drives depression onset.

Chronic stress is a major risk factor for depression onset. However, it remains unclear how repeated stress sculpts neural circuits and finally elicits depression. Given the essential role of lateral habenula (LHb) in depression, here, we attempt to clarify how LHb-centric neural circuitry integrates stress-related information. We identify lateral hypothalamus (LH) as the most physiologically relevant input to LHb under stress. LH neurons fire with a unique pattern that efficiently drives postsynaptic potential summation and a closely followed LHb bursting (EPSP-burst pairing) in response to various stressors. We found that LH-LHb synaptic potentiation is determinant in stress-induced depression. Mimicking this repeated EPSP-burst pairings at LH-LHb synapses by photostimulation, we artificially induced an "emotional status" merely by potentiating this pathway in mice. Collectively, these results delineate the spatiotemporal dynamics of chronic stress processing from forebrain onto LHb in a pathway-, cell-type-, and pattern-specific manner, shedding light on early interventions before depression onset.

Antihyperuricemia and antigouty arthritis effects of Persicaria capitata herba in mice.

BACKGROUND: Hyperuricemia (HUA) is an important risk factor for gout, renal dysfunction and cardiovascular diseases. The whole plant of Persicaria capitata (Buch.-Ham. ex D. Don) H. Gross, namely Persicaria capitata herba, is a well-known ethnic herb with potent therapeutic effects on urinary tract infections and urinary calculus, yet previous reports have only focused on its effect on urinary tract infections. PURPOSE: To evaluate the therapeutic potential of P. capitata herba against gout by investigating its antihyperuricemia and antigouty arthritis effects and possible mechanisms. METHODS: The ethanol extract (EP) and water extract (WP) of P. capitata herba were prepared by extracting dried and ground whole plants of P. capitata with 75% ethanol and water, respectively, followed by removal of solvents and characterization by UHPLC-Q-TOF/MS. The antihyperuricemia and antigouty arthritis effects of the two extracts were evaluated in a potassium oxonate- and hypoxanthine-induced hyperuricemia mouse model and a monosodium urate crystal (MSUC)-induced acute gouty arthritis mouse model, respectively. The mechanisms were investigated by testing their effects on the expression of correlated proteins (by Western blot) and mRNAs (by RT-PCR). RESULTS: UHPLC-HRMS fingerprinting and two chemical markers (i.e., quercetin and quercitrin) determination were used for the characterization of the WP and EP extracts. Both WP and EP extracts showed pronounced antihyperuricemia activities, with a remarkable decline in serum uric acid and a marked increase in urine uric acid in hyperuricemic mice. Unlike the clinical xanthine oxidase (XOD) inhibitor allopurinol, WP and EP did not show any distinct renal toxicities. The underlying antihyperuricemia mechanism involves the inhibition of the activity and expression of XOD and the downregulation of the mRNA and protein expression of glucose transporter 9 (GLUT9) and urate transporter 1 (URAT1). The extracts of P. capitata herba also demonstrated remarkable anti-inflammatory activity in MSUC-induced acute gouty arthritis mice. The mechanism might involve inhibitory effects on the expression of proinflammatory factors. CONCLUSIONS: The extracts of P. capitata herba possessed pronounced antihyperuricemia and antigouty arthritis effects and were, therefore, promising natural medicines for hyperuricemia-related disorders and gouty arthritis. The use of P. capitata herba for the treatment of urinary calculus may be, at least to some degree, related to its potential as an antihyperuricemia and antigouty arthritis drug.

Shuxuetong injection simultaneously ameliorates dexamethasone-driven vascular calcification and osteoporosis.

Osteoporosis (OP) and vascular calcification (VC) share a number of common risk factors, pathophysiological mechanisms and etiology, which are known as bone-vascular axis. The present study aimed to investigate the effects of Shuxuetong (SXT) injection on VC and osteoporosis. A rat model of VC and osteoporosis was induced by dexamethasone (DEX; 1 mg/kg/day for 4 weeks, intramuscularly). Simultaneously, 0.6 ml/kg/day SXT was intraperitoneally injected. Compared with control rats, DEX induced significantly more VC and OP, as determined by increased calcium deposition and alkaline phosphatase activity in the aorta, disturbed structure, decreased levels of cortical bone thickness and trabecular bone area, and increased apoptosis in the bone. SXT injection ameliorated DEX-induced VC and osteoporosis; furthermore, the osteoblastic differentiation of vascular smooth muscle cells and the activation of endoplasmic reticulum stress in the DEX group was also prevented by SXT injection. Compared with control rats, protein expression levels of sclerostin, a crucial crosslink of the bone-vascular axis, were significantly increased in the aorta and bone of rats with DEX, which was also attenuated by SXT injection. Thus, the present study suggested that SXT injection could ameliorate both VC and OP, and may be mediated by the regulation of sclerostin. The present study may provide the basis a novel strategy for the prevention and treatment of VC and OP, which emerge as side-effects of glucocorticoids.

New phenylpropanoid-substituted and benzyl-substituted flavonols from Alangium chinense.

Two previously undescribed flavonols with phenylpropanoid or benzyl substitution, named alangsine A (1), and alangsine B (2), together with four known compounds (3-6) were isolated from the leaves of Alangium chinense. Alangsine A was a racemic mixture, which was further separated into two enantiomers via high-performance liquid chromatography on a chiral column. The absolute configurations of the enantiomer pairs were deduced from the circular dichroism (CD) spectra. The activity of the isolated compounds towards neuronal excitability was examined.

Effect of Chinese herbal medicine compound on breast hyperplasia: A protocol of systematic review.

BACKGROUND: Data supporting the use of Chinese herbal medicine compound (CHMC) on breast hyperplasia (BH) based on the data from previous studies. However, the results are still contradictory. Thus, this study aims to compare the results obtained for effect on case-controlled study (CCS) of CHMC on BH. METHODS: This study will include CCS assessing the effect of CHMC on BH. A literature search will be carried out in Cochrane Library, MEDLINE, EMBASE, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from inception to the present. We will not apply language limitation to any electronic database. Study quality will be evaluated using Newcastle-Ottawa Scale, and statistical analysis will be performed using RevMan 5.3 software. RESULTS: This study will summarize the up-to-date evidence to assess the effect of CHMC on BH. CONCLUSION: The results of this study may exert helpful evidence to determine whether CHMC is effective on BH. OSF REGISTRATION NUMBER:: osf.io/3k8ch.

Integrated Network Pharmacology Analysis and Pharmacological Evaluation to Explore the Active Components and Mechanism of Abelmoschus manihot (L.) Medik. on Renal Fibrosis.

BACKGROUND: Renal fibrosis is a common pathological outcome of chronic kidney diseases (CKD) that is considered as a global public health issue with high morbidity and mortality. The dry corolla of Abelmoschus manihot (L.) Medik. (AMC) has been used for chronic nephritis in clinic and showed a superior effect in alleviating proteinuria in CKD patients to losartan. However, the effective components and underlying mechanism of AMC in the treatment of renal fibrosis have not been systematically clarified. METHODS: Based on drug-likeness evaluation, oral bioavailability prediction and compound contents, a systematic network pharmacology analysis was conducted to predict the active ingredients. Gene Ontology, Kyoto Encyclopedia of Genes and Genomes pathway analysis and protein-protein interaction analysis were applied to predict the potential pathway and target of AMC against renal fibrosis. The formula of component contribution index (CI) based on the algorithm was used to screen the principal active compounds of AMC in the treatment of renal fibrosis. Finally, pharmacological evaluation was conducted to validate the protective effect and primary predicted mechanism of AMC in the treatment of renal fibrosis on a 5/6 nephrectomy mice model. RESULTS: Fourteen potential active components of AMC possessing favorable pharmacokinetic profiles and biological activities were selected and hit by 17 targets closely related to renal fibrosis. Quercetin, caffeic acid, 9.12-octadecadienoic acid, and myricetin are recognized as the more highly predictive components as their cumulative contribution rate reached 85.86%. The AMC administration on 5/6 nephrectomy mice showed a protective effect on kidney function and renal fibrosis. The hub genes analysis revealed that AMC plays a major role in inhibiting epithelial-to-mesenchymal transition during renal fibrosis. CONCLUSION: Our results predicted active components and potential targets of AMC for the application to renal fibrosis from a holistic perspective, as well as provided valuable direction for further research of AMC and improved comprehension of renal fibrosis pathogenesis.