Effects of catechin on the stability of myofibrillar protein-soybean oil emulsion and the adsorbed properties of myosin at the oil-water interface.

The effects of different concentrations of catechin on the stability of myofibrillar protein-soybean oil emulsions and the related mechanisms were investigated. Adding 10 µmol/g catechin had no obvious effects on the emulsion stability and myosin structure, but 50, 100 and 200 µmol/g catechin decreased the emulsion stability. The microstructure observations showed that 10 µmol/g catechin caused a dense and uniform emulsion to form, whereas 50, 100 and 200 µmol/g catechin induced the merging of oil droplets. The addition of 50, 100 and 200 µmol/g catechin caused a decline in both the total sulfhydryl content and surface hydrophobicity, suggesting protein aggregation, which decreased the adsorption capacity of myosin and the elasticity of interfacial film. These results suggested that higher concentrations of catechin were detrimental to the emulsifying properties of myosin and that the dose should be considered when it is used as an antioxidant.

Cytokine Storm in Acute Viral Respiratory Injury: Role of Qing-Fei-Pai-Du Decoction in Inhibiting the Infiltration of Neutrophils and Macrophages through TAK1/IKK/NF-[Formula: see text]B Pathway.

COVID-19 has posed unprecedented challenges to global public health since its outbreak. The Qing-Fei-Pai-Du decoction (QFPDD), a Chinese herbal formula, is widely used in China to treat COVID-19. It exerts an impressive therapeutic effect by inhibiting the progression from mild to critical disease in the clinic. However, the underlying mechanisms remain obscure. Both SARS-CoV-2 and influenza viruses elicit similar pathological processes. Their severe manifestations, such as acute respiratory distress syndrome (ARDS), multiple organ failure (MOF), and viral sepsis, are correlated with the cytokine storm. During flu infection, QFPDD reduced the lung indexes and downregulated the expressions of MCP-1, TNF-[Formula: see text], IL-6, and IL-1[Formula: see text] in broncho-alveolar lavage fluid (BALF), lungs, or serum samples. The infiltration of neutrophils and inflammatory monocytes in lungs was decreased dramatically, and lung injury was ameliorated in QFPDD-treated flu mice. In addition, QFPDD also inhibited the polarization of M1 macrophages and downregulated the expressions of IL-6, TNF-[Formula: see text], MIP-2, MCP-1, and IP-10, while also upregulating the IL-10 expression. The phosphorylated TAK1, IKK[Formula: see text]/[Formula: see text], and I[Formula: see text]B[Formula: see text] and the subsequent translocation of phosphorylated p65 into the nuclei were decreased by QFPDD. These findings indicated that QFPDD reduces the intensity of the cytokine storm by inhibiting the NF-[Formula: see text]B signaling pathway during severe viral infections, thereby providing theoretical and experimental support for its clinical application in respiratory viral infections.

NIR/pH-triggered aptamer-functionalized DNA origami nanovehicle for imaging-guided chemo-phototherapy.

Targeted chemo-phototherapy has received widespread attention in cancer treatment for its advantages in reducing the side effects of chemotherapeutics and improving therapeutic effects. However, safe and efficient targeted-delivery of therapeutic agents remains a major obstacle. Herein, we successfully constructed an AS1411-functionalized triangle DNA origami (TOA) to codeliver chemotherapeutic drug (doxorubicin, DOX) and a photosensitizer (indocyanine green, ICG), denoted as TOADI (DOX/ICG-loaded TOA), for targeted synergistic chemo-phototherapy. In vitro studies show that AS1411 as an aptamer of nucleolin efficiently enhances the nanocarrier's endocytosis more than 3 times by tumor cells highly expressing nucleolin. Subsequently, TOADI controllably releases the DOX into the nucleus through the photothermal effect of ICG triggered by near-infrared (NIR) laser irradiation, and the acidic environment of lysosomes/endosomes facilitates the release. The downregulated Bcl-2 and upregulated Bax, Cyt c, and cleaved caspase-3 indicate that the synergistic chemo-phototherapeutic effect of TOADI induces the apoptosis of 4T1 cells, causing ~ 80% cell death. In 4T1 tumor-bearing mice, TOADI exhibits 2.5-fold targeted accumulation in tumor region than TODI without AS1411, and 4-fold higher than free ICG, demonstrating its excellent tumor targeting ability in vivo. With the synergetic treatment of DOX and ICG, TOADI shows a significant therapeutic effect of ~ 90% inhibition of tumor growth with negligible systemic toxicity. In addition, TOADI presents outstanding superiority in fluorescence and photothermal imaging. Taken together, this multifunctional DNA origami-based nanosystem with the advantages of specific tumor targeting and controllable drug release provides a new strategy for enhanced cancer therapy.

Reabsorption of intervertebral disc prolapse after conservative treatment with traditional Chinese medicine: A case report.

BACKGROUND: Conservative treatments have been reported to diminish or resolve clinical symptoms of lumbar intervertebral disc herniation (LIDH) within a few weeks. CASE SUMMARY: Computed tomography and magnetic resonance imaging (MRI) of the lumbar region of a 25-year-old male diagnosed with LIDH showed prolapse of the L5/S2 disc. The disc extended 1.0 cm beyond the vertebral edge and hung along the posterior vertebral edge. The patient elected a conservative treatment regimen that included traditional Chinese medicine (TCM), acupuncture, and massage. During a follow-up period of more than 12 mo, good improvement in pain was reported without complications. MRI of the lumbar region after 12 mo showed obvious reabsorption of the herniation. CONCLUSION: A conservative treatment regimen of TCM, acupuncture, and massage promoted reabsorption of a prolapsed disc.

Bio-inspired Oxidative Stress Amplifier for Suppressing Cancer Metastasis and Imaging-Guided Combination Therapy.

Antioxidant-defense systems of tumor cells protect them from oxidative damage and is strongly associated with tumor metastasis. In this work, a mussel-inspired multifunctional nanomedicine (ZS-MB@P) has been designed for inhibiting tumor growth and metastasis through amplified oxidative stress and photothermal/magnetothermal/photodynamic triple-combination therapy. This nanomedicine was fabricated via loading a silica shell on the magnetic nano-octahedrons [zinc-doped magnetic Fe3O4 nano-octahedrons] by encapsulating photosensitizer methylene blue (MB) and subsequently coating polydopamine (PDA) shells as "gatekeeper." The nanomedicine could realize photothermal therapy, photodynamic therapy, and magnetic hyperthermia after treatment with near-infrared (NIR) irradiation and applied magnetic field. Under pH and NIR stimulation, controlled amount of MB was released to produced exogenous reactive oxygen species. Noteworthy, PDA can amplify intracellular oxidative stress by depleting glutathione, thus inhibiting breast cancer metastasis effectively since oxidative stress is an important barrier to tumor metastasis. The outstanding ability to suppress tumor growth and metastasis was comprehensively assessed and validated both in vitro and in vivo. Moreover, the nanomedicine showed outstanding T2 magnetic resonance imaging for tracking the treatment process. Taken together, this work offers an innovative approach in the synergistic treatment of recalcitrant breast cancer.

Iridium Tungstate Nanozyme-Mediated Hypoxic Regulation and Anti-inflammation for Duplex Imaging Guided Photothermal Therapy of Metastatic Breast Tumors.

Metastasis of breast cancer is key to poor prognosis and high mortality. However, the excess reactive oxygen species (ROS) and inflammatory response induced by photothermal therapy (PTT) further aggravate tumor metastasis. Meanwhile, the hypoxic tumor microenvironment promotes tumor cells to metastasize to distant organs. Herein, the intrinsic limitations of PTT for metastatic tumor have been addressed by fabricating polyethylene glycol modified iridium tungstate (IrWOx-PEG) nanoparticles. The as-designed IrWOx-PEG nanoparticles displayed good photothermal (PT) conversion ability for duplex photoacoustic/PT imaging guided PTT and multienzyme mimetic feature for broad-spectrum ROS scavenging. On the one hand, IrWOx-PEG effectively removed excess ROS generated during PTT and reduced inflammation. On the other hand, owing to the catalase-like activity, it preferentially triggered the catalytic production of oxygen by decomposing ROS, leading to relieving of the hypoxic microenvironment. Hence, under bimodal imaging guidance, IrWOx-PEG induced PTT completely eliminated in situ breast cancer in 4T1 tumor-bearing mice with no observable system toxicity, as well as further restricting tumor metastasis to other vital organs (lungs) by ROS scavenging, anti-inflammation, and regulating hypoxic microenvironment. We anticipate that this work will lead to new treatment strategies for other metastatic cancers.

[Reduning Injection protects flu-infected mice by inhibiting infiltration of inflammatory cells in lung and down-regulating cytokine storm].

This study aimed to explore the protective effect of Reduning Injection(RDN) on mice infected by influenza virus A/PR/8(PR8) and its immune regulatory roles during viral infection. In in vivo experiments, female C57 BL/6 mice were randomly divided into phosphate buffered saline(PBS) group, PR8-infected group, oseltamivir treatment group(OSV) and RDN treatment group. After 2 h of PR8 infection, mice in the oseltamivir group were gavaged with oseltamivir 30 mg·kg~(-1), and those in the RDN treatment group were injected intraperitoneally with RDN 1.5 mL·kg~(-1)once per day for seven consecutive days. The body weight of mice in each group was recorded at the same time every morning for 16 consecutive days. The line chart of body weight change was created to analyze the protective effect of RDN on flu-infected mice. The relative mRNA expression of different cytokines(IL-6, TNF-α, MCP-1, IL-1ß, MIP-2, IP-10 and IL-10) in lung samples of flu-infected mice was detected by PCR. Flow cytometry was utilized to analyze the composition of immune cells of mouse BALF samples on day 5 after infection. Mouse macrophage cell line RAW264.7 was planted and treated by different concentrations of RDN(150, 300, 600 µg·mL~(-1)) for 24 h or 48 h, and cell proliferation was detected by CCK-8 assay. RAW264.7 cells and mouse primary peritoneal macrophages were stimulated with synthetic single stranded RNA(R837), which elicited the inflammatory response by mimicking the infection of single-stranded RNA viruses. The expression of cytokines and chemokines in the supernatants of above culture system was detected by ELISA and qPCR. On days 4, 5, 6, 7 and 15 after infection, the body weight loss of mice in the RDN treatment group was alleviated compared with that of PR8-infected mice(P<0.05). RDN treatment obviously reduced lung index and the production of IL-6, TNF-α, MCP-1 and MIP-2 in lung tissues of flu-infected mice(P<0.05). The proportions of macrophages, neutrophils and T cells in mouse BALF samples were analyzed by flow cytometry, and compared with PR8-infected mice, RDN decreased the proportion of macrophages in BALF of flu-infected mice(P<0.05), and the proportion of T cells was recovered dramatically(P<0.001). In CCK-8 assay, the concentrations of RDN(150, 300, 600 µg·mL~(-1)) failed to cause cytotoxicity to RAW264.7 cells. In addition, RDN lowered the expression of inflammatory cytokines such as IL-6, TNF-α,MCP-1, IL-1ß, RANTES, and IP-10 and even anti-inflammatory cytokine IL-10 in R837-induced macrophages. RDN reduced the infiltration of inflammatory macrophages and the production of excessive inflammatory cytokines, alleviated the body weight loss of flu-infected mice. What's more, RDN restored the depletion of T cells, which might prevent secondary infection and deteriorative progression of the disease. Taken together, RDN may inhibit cytokine production and therefore down-regulate cytokine storm during the infection of influenza virus.

Effects and Mechanisms of Rhus chinensis Mill. Fruits on Suppressing RANKL-Induced Osteoclastogenesis by Network Pharmacology and Validation in RAW264.7 Cells.

Rhus chinensis Mill. fruits are a kind of widely distributed edible seasoning, which have been documented to possess a variety of biological activities. However, its inhibitory effect on osteoclast formation has not been determined. The objective of this study was to evaluate the effect of the fruits on osteoclast differentiation of RAW264.7 cells, induced by receptor activator of nuclear factor-κB ligand (RANKL) and to illuminate the potential mechanisms using network pharmacology and western blots. Results showed that the extract containing two organic acids and twelve phenolic substances could effectively inhibit osteoclast differentiation in RANKL-induced RAW264.7 cells. Network pharmacology examination and western blot investigation showed that the concentrate essentially decreased the expression levels of osteoclast-specific proteins, chiefly through nuclear factor kappa-B, protein kinase B, and mitogen-activated protein kinase signaling pathways, particularly protein kinase B α and mitogen-activated protein kinase 1 targets. Moreover, the extract likewise directly down regulated the expression of cellular oncogene Fos and nuclear factor of activated T-cells cytoplasmic 1 proteins. Citric acid, quercetin, myricetin-3-O-galactoside, and quercetin-3-O-rhamnoside were considered as the predominant bioactive ingredients. Results of this work may provide a scientific basis for the development and utilization of R. chinensis fruits as a natural edible material to prevent and/or alleviate osteoporosis-related diseases.

(-)-Naringenin 4',7-dimethyl Ether Isolated from Nardostachys jatamansi Relieves Pain through Inhibition of Multiple Channels.

(-)-Naringenin 4',7-dimethyl ether ((-)-NRG-DM) was isolated for the first time by our lab from Nardostachys jatamansi DC, a traditional medicinal plant frequently used to attenuate pain in Asia. As a natural derivative of analgesic, the current study was designed to test the potential analgesic activity of (-)-NRG-DM and its implicated mechanism. The analgesic activity of (-)-NRG-DM was assessed in a formalin-induced mouse inflammatory pain model and mustard oil-induced mouse colorectal pain model, in which the mice were intraperitoneally administrated with vehicle or (-)-NRG-DM (30 or 50 mg/kg) (n = 10 for each group). Our data showed that (-)-NRG-DM can dose dependently (30~50 mg/kg) relieve the pain behaviors. Notably, (-)-NRG-DM did not affect motor coordination in mice evaluated by the rotarod test, in which the animals were intraperitoneally injected with vehicle or (-)-NRG-DM (100, 200, or 400 mg/kg) (n = 10 for each group). In acutely isolated mouse dorsal root ganglion neurons, (-)-NRG-DM (1~30 µM) potently dampened the stimulated firing, reduced the action potential threshold and amplitude. In addition, the neuronal delayed rectifier potassium currents (IK) and voltage-gated sodium currents (INa) were significantly suppressed. Consistently, (-)-NRG-DM dramatically inhibited heterologously expressed Kv2.1 and Nav1.8 channels which represent the major components of the endogenous IK and INa. A pharmacokinetic study revealed the plasma concentration of (-)-NRG-DM is around 7 µM, which was higher than the effective concentrations for the IK and INa. Taken together, our study showed that (-)-NRG-DM is a potential analgesic candidate with inhibition of multiple neuronal channels (mediating IK and INa).

Isolation and identification of two new sargentodoxosides from Sargentodoxa cuneata and their agonistic effects against FXR.

Sargentodoxa cuneata (Oliv.) Rehd. et Wils is a traditional Chinese medicine to treat acute appendicitis, rheumarthritis, abdominal pain, and painful menstruation for a long history. The investigation of S. cuneata led to the isolation and identification of twenty-three secondary metabolites, including two new compounds, sargentodoxosides A (1) and B (2), and twenty-one known ones (3-23). Their structural characterization was conducted by HRESIMS, 1 D and 2 D NMR spectra. All the isolated compounds were assayed for their agonistic activities against the farnesoid X receptor (FXR). Nine of the isolated compounds displayed significant agonistic effects against FXR at 0.1 µM, suggesting that they could be served as potential agents for the development of FXR agonists.

A new product of multi-plant extracts improved skin photoaging: An oral intake in vivo study.

BACKGROUND: Besides the topical application of cosmetics, nutraceuticals represent a promising strategy for preventing skin photoaging and skin cancers. METHODS: To determine the effect of a new multi-plant extracts product containing Cucumis melo extract, acerola extract, olive fruit, aloe vera gel, grape seed extract, and lycopene, a randomized, placebo-controlled, double-blind clinical trial and an ultraviolet (UV)-induced murine photoaging model were deployed. 55 healthy subjects aged 45-60 were enrolled and randomized to take the product or placebo orally for 12 weeks. Skin aging and whitening indexes were measured with non-invasive techniques. 90 Balb/c mice aged 7-8 weeks were randomly divided into six groups: normal, UV, UV+vehicle, UV+different doses of the product (0.500 g/kg.BW, 0.250 g/kg.BW, 0.125 g/kg.BW, respectively). Except the normal group, mid-dorsal regions were irradiated with UVA+UVB for 8 weeks. Factors of oxidative stress, tyrosinase, and histological analysis of the mid-dorsal skin were determined. RESULTS: In the clinical trial, the TEWL, hydration, sebum, elasticity, and the L*, a*, melanin index change from baseline, ITA° were significantly improved in the experiment group. In the animal experiment, compared to the UV+vehicle group, UV+high dose group showed significantly lower malondialdehyde (MDA) and tyrosinase, but higher superoxide dismutase (SOD), total antioxidant capacity (T-AOC), and glutathione peroxidase (GSH-Px). The UV+moderate dose group showed significant improvement of MDA and GSH-Px, and the UV+low dose group only showed improvement of GSH-Px. Histological photoaging manifestations were attenuated in the UV+high and moderate dose groups. CONCLUSIONS: The multi-plant extracts product improved skin photoaging possibly via antioxidant and anti-tyrosinase ways.

Effects of chitooligosaccharide-zinc on the ovarian function of mice with premature ovarian failure via the SESN2/NRF2 signaling pathway.

Chitooligosaccharide-zinc (COS·Zn) is a powerful anti-oxidant and anti-aging scavenger, whose anti-oxidative ability immensely exceeds vitamin C. Therefore, this study was aimed to investigate the protective effects of COS·Zn against premature ovarian failure (POF) and potential mechanisms. Female KM adult mice were divided into the following groups: a treatment group (150 mg·kg-1·d-1 COS·Zn), a treatment group (300 mg·kg-1·d-1 COS·Zn), a prevention group, two control groups and two CY/BUS groups. COS·Zn (150, 300 mg·kg-1·d-1) and COS·Zn (300 mg·kg-1·d-1) were therapeutically and preventatively administered to POF mice in the treatment and prevention studies, respectively. All the groups were administered for 21 days. Fewer primary and secondary follicles were observed in the COS·Zn-treated groups (including the treatment and prevention groups) than those of the control groups. Meanwhile, the ovarian index and the levels of FSH and LH notably increased in the treatment and prevention groups compared with those in the CY/BUS group. The levels of MVH, OCT4 and PCNA in the treatment group (300·kg-1·d-1 COS·Zn) and MVH in the prevention group remarkably increased compared with those in the CY/BUS groups. Meanwhile, the levels of P53 and P16 protein were down-regulated in the treatment and prevention groups compared with those in the CY/BUS groups. Additionally, the amounts of Sestrin2 (SESN2) and SOD2 protein were obviously higher in the treatment group (150 mg·kg-1·d-1 COS·Zn) than those in the CY/BUS groups. Similarly, the amounts of NRF2 and SESN2 protein were up-regulated in the prevention group. Besides, an increased GSH level was observed in the two treatment groups, compared with that in the CY/BUS groups, and the same trend was also present in the prevention group. Taken together, COS·Zn improves the ovarian and follicular development through regulating the SESN2/NRF2 signaling pathway. These results suggest the role of COS·Zn as a novel agent for the treatment and prevention of POF.

Assessment of Skin Photoallergy Risk in Cosmetics Containing Herbal Extract Ingredients.

BACKGROUND/OBJECTIVE: In recent years, herbal extracts are becoming increasingly popular ingredients added in cosmetics; however, the assessment of their potential adverse effects on the skin remains unclear. As Coptis, Phellodendron amurense, curcumin, and shikonin are herbs currently used in cosmetic ingredients, the aim of this study was to assess their skin photoallergy (PA) potential and the concentrations at which they could safely be used. METHODS: In the patch test, Coptis, P. amurense, curcumin, and shikonin with 5, 10, 25, and 50% concentration were applied on 33 healthy Chinese subjects using the T.R.U.E. TEST® patch test system for 48 h. Photopatch testing was performed on 206 Chinese subjects with predisposed photosensitivity history using the Scandinavian photopatch series, and subjects were irradiated by 50% UVA minimum erythema dose. Photopatch testing of herbal extracts was then performed on subjects diagnosed with PA. RESULTS: Thirty-three subjects (14 with type III skin and 19 with type IV skin) completed contact patch testing of herbal extracts. Coptis induced a contact allergy (CA) reaction on 2 subjects at 25% concentration and on 2 subjects at 10% concentration. P. amurense induced a CA reaction on 1 subject at 10% concentration and on 1 subject at 5% concentration. Shikonin induced a stimulating reaction on 1 subject at 10% concentration. Curcumin induced a stimulating reaction on 1 subject at 10% concentration. Of the 206 Chinese subjects predisposed for photosensitivity, 10.19% had PA, 16.5% showed CA, and 1.45% had both PA + CA. PA-induced substances were promethazine hydrochloride (15%, n = 31), chlorpromazine hydrochloride (10.84%, n = 19), perfume mix (5.82%, n = 12), atranorin (3.39%, n = 7), 6-methyl coumarine (3.39%, n = 7), balsam Peru (1.94%, n = 4), fentichlor (1.94%, n = 4), 3,3',4',5-tetrachloro salicylanilide (0.97%, n = 2), hexachlorophene (0.97%, n = 2), chlorhexidine digluconate (0.97%, n = 2), and 4-aminobenzoic acid 2-hydroxy-4-methoxybenzophenone (0.97%, n = 2). Coptis at 25, 10, and 5% concentration and P. amurense, shikonin, and curcumin each at 10 and 5% concentration induced negative photopatch test results in all 10 photosensitive subjects. CONCLUSION: We have shown that Coptis, shikonin, or curcumin at 5% concentration in cosmetics could be applied safely without inducing contact allergic and photosensitive reactions on the skin. These findings advance the understanding of herbal extract use in cosmetic ingredients as related to the fields of dermatopharmacology and dermatotoxicology.

Apigenin inhibits the growth of colorectal cancer through down-regulation of E2F1/3 by miRNA-215-5p.

BACKGROUND: Apigenin (API) is a naturally occurring plant-derived flavone, which is abundantly present in common fruits and vegetables, and shows little or no toxicity of daily diet. The treatment of colorectal cancer is limited by high recurrence rate and multidrug resistance. PURPOSE: The purpose of this study was to explore the potential therapeutic effect and possible mechanisms of API on colorectal cancer cells. METHODS: Cell proliferation and apoptosis of human colon cancer cell line HCT116 was assessed after API treatment. A comprehensive transcriptome profile of API-treated HCT116 cells was acquired by high-throughput sequencing. The regulation of miRNA215-5p and E2F1/3 were identified by bioinformatics analyses. An inhibitor of miRNA215-5p, inhibitor 215, was applied to confirm the role of this microRNA played in the anti-cancer effect of API. Luciferase reporter gene assay was performed to identify targeting relationship between miRNA215-5p and E2F1/3. RESULT: API significantly promoted cell apoptosis and anti-proliferation of HCT116 cells in a dose-dependent manner. Bioinformatics analyses identified several altered miRNAs among which the expression of miRNA-215-5p showed markedly increased. Meanwhile, the expression of E2F1 and E2F3 was decreased by API, which was associated with miRNA215-5p. Luciferase reporter gene assay showed miRNA-215-5p could directly bind to 3' UTR of E2F1/3. Inhibition of miRNA-215-5p significantly inhibited apoptosis and cell cycle arrest at G0/G1 phase induced by API. CONCLUSIONS: The result of this study confirmed the anti-cancer effect of API on human colorectal cancer cells and investigated the underlying mechanism by a comprehensive transcriptome profile of API-treated cells.

Active Components from Cassia abbreviata Prevent HIV-1 Entry by Distinct Mechanisms of Action.

Cassia abbreviata is widely used in Sub-Saharan Africa for treating many diseases, including HIV-1 infection. We have recently described the chemical structures of 28 compounds isolated from an alcoholic crude extract of barks and roots of C. abbreviata, and showed that six bioactive compounds inhibit HIV-1 infection. In the present study, we demonstrate that the six compounds block HIV-1 entry into cells: oleanolic acid, palmitic acid, taxifolin, piceatannol, guibourtinidol-(4α→8)-epiafzelechin, and a novel compound named as cassiabrevone. We report, for the first time, that guibourtinidol-(4α→8)-epiafzelechin and cassiabrevone inhibit HIV-1 entry (IC50 of 42.47 µM and 30.96 µM, respectively), as well as that piceatannol interacts with cellular membranes. Piceatannol inhibits HIV-1 infection in a dual-chamber assay mimicking the female genital tract, as well as HSV infection, emphasizing its potential as a microbicide. Structure-activity relationships (SAR) showed that pharmacophoric groups of piceatannol are strictly required to inhibit HIV-1 entry. By a ligand-based in silico study, we speculated that piceatannol and norartocarpetin may have a very similar mechanism of action and efficacy because of the highly comparable pharmacophoric and 3D space, while guibourtinidol-(4α→8)-epiafzelechin and cassiabrevone may display a different mechanism. We finally show that cassiabrevone plays a major role of the crude extract of CA by blocking the binding activity of HIV-1 gp120 and CD4.

Comparative study on the antituberculous effect and mechanism of the traditional Chinese medicines NiuBeiXiaoHe extract and JieHeWan.

BACKGROUND: The traditional Chinese medicine NiuBeiXiaoHe (NBXH) extract and Chinese medicine preparation JieHeWan (JHW) exhibit anti-tuberculosis effects. The anti- tuberculosis effect of NBXH was compared with that of JHW to elucidate the mechanism of action of NBXH. METHODS: BALB/c mice aged 6-8 weeks were randomly divided into a normal control group, Tuberculosis (TB) model group, JHW treatment group, and NBXH treatment group. After 3 and 13 weeks of treatment, the therapeutic effect in each group was evaluated by comparing lung histopathology, lung and liver colony counts, the number of spots representing effector T cells secreting IFN-γ in an ELISPOT, and the levels of Th1, Th2, and Th17 cytokines, which were measured by a cytometric bead array (CBA). Mouse RNA samples were subjected to transcriptome sequencing. RESULTS: After 13 weeks of treatment, the mean histopathological lesion area of the NBXH group was significantly smaller than that of the TB model group (P < 0.05). Compared with those in the TB model group, the lung colony counts in the JHW and NBXH groups were significantly decreased (P < 0.05), and the IL-2 and IL-4 levels in the NBXH group were significantly increased (P < 0.05). NBXH partly restored significant changes in gene expression caused by Mycobacterium tuberculosis (M. tuberculosis) infection. According to GO and KEGG analyses, the changes in biological process (BP), cell composition (CC) and molecular function (MF) terms and in signaling pathways caused by NBXH and JHW treatment were not completely consistent, but they were mainly related to the immune response and inflammatory response in the mouse TB model. CONCLUSIONS: NBXH had therapeutic effects similar to those of JHW in improving lung histopathology, reducing lung colony counts, and regulating the levels of cytokines. NBXH restored significant changes in gene expression and repaired cell damage caused by M. tuberculosis infection by regulating immune-related pathways, which clarified the mechanism of action of NBXH.

Chemical Constituents of Cassia abbreviata and Their Anti-HIV-1 Activity.

Three new (1-3) and 25 known compounds were isolated from the crude extract of Cassia abbreviata. The chemical structures of new compounds were established by extensive spectroscopic analyses including 1D and 2D NMR and HRESIMS. Cassiabrevone (1) is the first heterodimer of guibourtinidol and planchol A. Compound 2 was a new chalcane, while 3 was a new naphthalene. Cassiabrevone (1), guibourtinidol-(4α→8)-epiafzelechin (4), taxifolin (8), oleanolic acid (17), piceatannol (22), and palmitic acid (28), exhibited potent anti-HIV-1 activity with IC50 values of 11.89 µM, 15.39 µM, 49.04 µM, 7.95 µM, 3.58 µM, and 15.97 µM, respectively.

Cassane diterpenoid derivative induces apoptosis in IDH1 mutant glioma cells through the inhibition of glutaminase in vitro and in vivo.

BACKGROUND: Glioblastoma multiforme (GBM) is the most frequent, lethal and aggressive tumour of the central nervous system in adults. The discovery of novel anti-GBM agents based on the isocitrate dehydrogenase (IDH) mutant phenotypes and classifications have attracted comprehensive attention. PURPOSE: Diterpenoids are a class of naturally occurring 20-carbon isoprenoid compounds, and have previously been shown to possess high cytotoxicity for a variety of human tumours in many scientific reports. In the present study, 31 cassane diterpenoids of four types, namely, butanolide lactone cassane diterpenoids (I) (1-10), tricyclic cassane diterpenoids (II) (11-15), polyoxybutanolide lactone cassane diterpenoids (III) (16-23), and fused furan ring cassane diterpenoids (IV) (24-31), were tested for their anti-glioblastoma activity and mechanism underlying based on IDH1 mutant phenotypes of primary GBM cell cultures and human oligodendroglioma (HOG) cell lines. RESULTS: We confirmed that tricyclic-type (II) and compound 13 (Caesalpin A, CSA) showed the best anti-neoplastic potencies in IDH1 mutant glioma cells compared with the other types and compounds. Furthermore, the structure-relationship analysis indicated that the carbonyl group at C-12 and an α, ß-unsaturated ketone unit fundamentally contributed to enhancing the anti-glioma activity. Studies investigating the mechanism demonstrated that CSA induced oxidative stress via causing glutathione reduction and NOS activation by negatively regulating glutaminase (GLS), which proved to be highly dependent on IDH mutant type glioblastoma. Finally, GLS overexpression reversed the CSA-induced anti-glioma effects in vitro and in vivo, which indicated that the reduction of GLS contributed to the CSA-induced proliferation inhibition and apoptosis in HOG-IDH1-mu cells. CONCLUSION: Therefore, the present results demonstrated that compared with other diterpenoids, tricyclic-type diterpenoids could be a targeted drug candidate for the treatment of secondary IDH1 mutant type glioblastoma through negatively regulating GLS.

The Protective Effect of Rosavin from Rhodiola rosea on Radiation-Induced Intestinal Injury.

Bioactive constituents from Rhodiola rosea L. (RRL) exhibit multiple pharmacological effects on diverse diseases. However, whether they are suitable for the treatment of radiation-induced intestinal injury (RIII) remains unclear. This study aims to investigate their roles and mechanisms in the RIII rat model. The radioprotective effects of the four bioactive constituents of RRL (salidroside, herbacetin, rosavin and arbutin) were evaluated by the cell viability of irradiated IEC-6 cells. Intestinal tissues were collected for histological analysis, localized inflammation and oxidative stress assessments. Our work showed that salidroside, rosavin and arbutin improved the cell viability of the irradiated IEC-6 cells, with the highest improvement in 12.5 µM rosavin group. The rosavin treatment significantly improved survival rate and intestinal damage in irradiated rats by modulating the inflammatory response and oxidative stress. Our work indicated that rosavin may be the optimal constituent of RRL for RIII treatment, providing an attractive candidate for radioprotection.

Recoding the Cancer Epigenome by Intervening in Metabolism and Iron Homeostasis with Mitochondria-Targeted Rhenium(I) Complexes.

The development and malignancy of cancer cells are closely related to the changes of the epigenome. In this work, a mitochondria-targeted rhenium(I) complex (DFX-Re3), integrating the clinical iron chelating agent deferasirox (DFX), has been designed. By relocating iron to the mitochondria and changing the key metabolic species related to epigenetic modifications, DFX-Re3 can elevate the methylation levels of histone, DNA, and RNA. As a consequence, DFX-Re3 affects the events related to apoptosis, RNA polymerases, and T-cell receptor signaling pathways. Finally, it is shown that DFX-Re3 induces immunogenic apoptotic cell death and exhibits potent antitumor activity in vivo. This study provides a new approach for the design of novel epigenetic drugs that can recode the cancer epigenome by intervening in mitochondrial metabolism and iron homeostasis.