Guided isolation of secondary metabolites from Nectria sp. MHHJ-3 by molecular network strategy.

The fungus Nectria sp. MHHJ-3 was isolated from Illigera rhodantha. A molecular networking-guided the secondary metabolites investigation of Nectria sp. MHHJ-3 led to the isolation of ten metabolites (1-10), including two new naphthalenone derivatives, nectrianaphthalenones A (1) and B (2), and two new steroids, nectriasteroids A (3) and B (4). Their structures were elucidated by extensive spectroscopic analysis including the HRESIMS, 1D/2D NMR and electronic circular dichroism (ECD) spectra. A plausible biosynthetic pathway for 1-2 was proposed. Compounds 1 and 2 exhibited moderate acetylcholinesterase (AChE) inhibitory activities. Compounds 3 and 4 showed significant cytotoxic activity against selected tumor cells. Particularly, compound 3 exhibited the strongest activity against A549 cells with an IC50 value of 13.73 ± 0.03 µM, which was at the same grade with that of positive control cisplatin.

Effect of Baduanjin Qigong Exercise on Cancer-Related Fatigue in Patients with Colorectal Cancer Undergoing Chemotherapy: A Randomized Controlled Trial.

BACKGROUND: Cancer-related fatigue (CRF) is one of the most troubling symptoms of cancer patients during chemotherapy, and no gold standard for the treatment of CRF has been established. OBJECTIVE: This study aimed to examine the effects of the Baduanjin qigong on patients with colorectal cancer and CRF, and to explore its intervention effects. METHODS: This was an open-label, randomized controlled clinical trial. Ninety patients with chemotherapy-treated colorectal cancer and CRF were randomized to a Baduanjin exercise group or a routine care group. The primary outcome was the Brief Fatigue Inventory (BFI) score at 24 weeks. The secondary outcomes were the Karnofsky Performance Status (KPS) and Pittsburgh Sleep Quality Index (PSQI) scores at 24 weeks. RESULTS: There were no significant differences between the two groups in CRF level at baseline and 12 weeks. At 24 weeks, the proportion of patients with moderate-to-severe CRF was significantly smaller in the exercise group than in the control group (23.2 vs. 59.1%, p < 0.01). The KPS and PSQI scores were similar in the two groups at baseline and 12 weeks, but they were significantly higher and lower, respectively, at 24 weeks in the exercise group compared with the control group (KPS score: 89.3 ± 8.3 vs. 75.2 ± 11.5, p < 0.01; PSQI score: 4.1 ± 1.1 vs. 6.9 ± 2.0, p < 0.01). Significant time-group interactions were observed for all three scores (all p < 0.01). CONCLUSIONS: Baduanjin qigong exercise can relieve CRF in patients with colorectal cancer undergoing chemotherapy and can improve their physical activity level and their quality of sleep.

Comparison of anti-inflammatory effects of berberine, and its natural oxidative and reduced derivatives from Rhizoma Coptidis in vitro and in vivo.

BACKGROUND: Berberine (BBR) is the most abundant and major active constituent of Rhizoma Coptidis (RC), which has been widely used to treat inflammatory diseases in traditional oriental medicine. Despite BBR has been found to exhibit pronounced anti-inflammatory effect, the anti-inflammatory activities of its natural derivatives were sparsely dissected out. PURPOSE: To comparatively investigate the anti-inflammatory potential of BBR, and its natural oxoderivative (oxyberberine, OBB) and reduced derivative (dihydroberberine, DHBB) in vitro and in vivo, and delineate the possible underlying mechanism. METHODS: LC-MS/MS was used to identify the natural derivatives of BBR in RC. The potential anti-inflammatory properties of BBR and its natural derivatives were comparatively evaluated in vitro by lipopolysaccharide (LPS)-induced RAW264.7 macrophages cells, and in vivo via three typical acute inflammation murine models. Some important inflammation-related molecules were analyzed by ELISA, qRT-PCR and Western blotting. RESULTS: LC-MS/MS led to the identification of BBR, OBB and DHBB in RC ethyl acetate extract. The in vitro assay indicated that BBR, OBB and DHBB (1.25, 2.5 and 5 µM) pretreatment significantly decreased the levels of pro-inflammatory cytokines tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), interleukin-6 (IL-6), prostaglandinE2 (PGE2) and nitricoxide (NO), and inhibited the mRNA expressions of cyclooxygenase-2 (COX-2) and inducible nitricoxide synthase (iNOS) in a dose-dependent manner, with relative efficiency of OBB > BBR > DHBB. Furthermore, OBB, BBR and DHBB remarkably inhibited the phosphorylation of nuclear factor-κB (NF-κB) p65 and inhibitory kappa Bα (IκBα). In vivo, BBR (20 mg/kg) and OBB (5, 10, and 20 mg/kg) pretreatment significantly ameliorated the xylene-induced ear edema, carrageenan-stimulated paw edema, and acetic acid-elicited vascular permeability in mice in a dose-dependent manner, with OBB exhibiting superior anti-inflammatory effect at the same dose (20 mg/kg). Histopathological analysis indicated that OBB and BBR could markedly attenuate the inflammatory deterioration and decrease the cellular infiltration in paw tissues. Additionally, the carrageenan-induced increases in TNF-α, IL-6, IL-1ß, PGE2 and NO productions, and COX-2 and iNOS mRNA expressions were effectually and concentration-dependently suppressed by OBB and BBR pretreatment. CONCLUSION: The anti-inflammatory activity of BBR and its natural derivatives was in the order of OBB > BBR > DHBB. OBB was for the first time found to be endowed with pronounced anti-inflammatory property, which was probably associated with suppressing the activation of NF-κB signaling pathway, and the subsequent gene expressions and productions of pro-inflammatory mediators. The results might contribute to illuminating the pharmacodynamic underpinnings of RC and provide evidence for developing OBB as a safe and promising natural lead compound in inflammation treatment.

Therapeutic efficacy and safety of Kang-ai injection combined with platinum-based doublet chemotherapy in advanced NSCLC: A meta-analysis.

AIMS: Kang-ai injection (KA) is a famous Chinese patent medicine authorized by China Food and Drug Administration, which is widely used to treat advanced non-small cell lung cancer (NSCLC) in China. This meta-analysis is aimed to evaluate the therapeutic efficacy and safety of KA on advanced NSCLC. METHODS: Seven databases were examined for related studies until January 15, 2018. Odds ratio (OR) was used to evaluate tumor response, Karnofsky Performance Scale (KPS) improvement and adverse reactions, and mean difference (MD) was used to estimate immune functions. KEY FINDINGS: Thirty randomized controlled trials involving 1956 patients with advanced NSCLC were included. The results showed that compared with the platinum-based doublet chemotherapy (PBDC) alone, KA combined with PBDC could significantly enhance tumor response (OR = 1.69, 95% CI [1.40, 2.04], P < 0.00001), KPS improvement (OR = 3.01, 95% CI [2.36, 3.84], P < 0.00001) and immune functions including the percentages of CD3+ (MD = 8.90, 95% CI [3.06, 14.73], P = 0.003), CD4+ (MD = 9.43, 95% CI [6.32, 12.53], P < 0.00001) and NK (MD = 4.81, 95% CI [1.95, 7.68], P = 0.001) and the ratio of CD4+/CD8+ (MD = 0.29, 95% CI [0.04, 0.53], P = 0.02). Moreover, KA combined with PBDC markedly decreased the incidences of adverse reactions including gastrointestinal reaction (OR = 0.38, 95% CI [0.30, 0.47], P < 0.00001), myelosuppression (OR = 0.32, 95% CI [0.23, 0.45], P < 0.00001) and hair loss (OR = 0.53, 95% CI [0.36, 0.76], P < 0.00001). However, there was no significant difference between the combination treatment group and the control group in the percentage of CD8+ (MD = -2.93, 95% CI [-6.68, 0.82], P = 0.13). SIGNIFICANCE: Despite the small sample size and study limitations, the results of this meta-analysis indicated that the combination therapy of KA and PBDC (especially NP regimen) might be a beneficial therapeutic method for advanced NSCLC patients.

ß-Patchoulene from patchouli oil protects against LPS-induced acute lung injury via suppressing NF-κB and activating Nrf2 pathways.

ß-Patchoulene (ß-PAE), a tricyclic sesquiterpene isolated from the essential oil of the leaves and stems of Pogostemon cablin (Blanco) Benth., has been reported to have potent anti-inflammatory activity. The aim of this study was to evaluate the potential protective effect of ß-PAE on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and to illuminate the underlying mechanisms. ALI was induced by intracheal instillation of LPS into lung, and dexamethasone (DEX) was used as a positive control. Results indicated that pretreatment with ß-PAE significantly decreased the mortality rate of mice and lung W/D weight ratio, ameliorated lung pathological changes as compared to model group. Meanwhile, ß-PAE pretreatment markedly inhibited the increase of TNF-α, IL-6 and IL-1ß secretions in the bronchoalveolar lavage fluid, and prevented LPS-induced elevations of MPO activity and MDA level in the lung. Additionally, ß-PAE pretreatment significantly elevated miR-146a expression and suppressed the LPS-induced activation of NF-κB and expression of its mediated genes (TNF-α, IL-6 and IL-1ß). ß-PAE was also observed to markedly upregulate the Nrf2 and HO-1 expression and activate the antioxidant genes (NQO-1, GCLC and HO-1). Taken together, ß-PAE possessed protective effect against LPS-induced ALI, which might be associated with its differential regulation of NF-κB and Nrf2 activities and up-regulation of expression of miR-146a. The results rendered ß-PAE a promising anti-inflammatory agent worthy of further development into a pharmaceutical drug for the treatment of ALI.

Inhibition of Helicobacter pylori and Its Associated Urease by Palmatine: Investigation on the Potential Mechanism.

In this paper, we evaluated the anti-Helicobacter pylori activity and the possible inhibitory effect on its associated urease by Palmatine (Pal) from Coptis chinensis, and explored the potential underlying mechanism. Results indicated that Pal exerted inhibitory effect on four tested H. pylori strains (ATCC 43504, NCTC 26695, SS1 and ICDC 111001) by the agar dilution test with minimum inhibitory concentration (MIC) values ranging from 100 to 200 µg/mL under neutral environment (pH 7.4), and from 75 to 100 µg/mL under acidic conditions (pH 5.3), respectively. Pal was observed to significantly inhibit both H. pylori urease (HPU) and jack bean urease (JBU) in a dose-dependent manner, with IC50 values of 0.53 ± 0.01 mM and 0.03 ± 0.00 mM, respectively, as compared with acetohydroxamic acid, a well-known urease inhibitor (0.07 ± 0.01 mM for HPU and 0.02 ± 0.00 mM for JBU, respectively). Kinetic analyses showed that the type of urease inhibition by Pal was noncompetitive for both HPU and JBU. Higher effectiveness of thiol protectors against urease inhibition than the competitive Ni2+ binding inhibitors was observed, indicating the essential role of the active-site sulfhydryl group in the urease inhibition by Pal. DTT reactivation assay indicated that the inhibition on the two ureases was reversible, further supporting that sulfhydryl group should be obligatory for urease inhibition by Pal. Furthermore, molecular docking study indicated that Pal interacted with the important sulfhydryl groups and inhibited the active enzymatic conformation through N-H ∙ π interaction, but did not interact with the active site Ni2+. Taken together, Pal was an effective inhibitor of H. pylori and its urease targeting the sulfhydryl groups, representing a promising candidate as novel urease inhibitor. This investigation also gave additional scientific support to the use of C. chinensis to treat H. pylori-related gastrointestinal diseases in traditional Chinese medicine. Pal might be a potentially beneficial therapy for gastritis and peptic ulcers induced by H. pylori infection and other urease-related diseases.

Protective Effect of SFE-CO2 of Ligusticum chuanxiong Hort Against d-Galactose-Induced Injury in the Mouse Liver and Kidney.

This study was designed to explore how supercritical fluid CO2 extract of Ligusticum chuanxiong Hort (CX) protects mouse liver and kidney from d-galactose-induced injury. The antioxidant capacity of CX was confirmed both in vitro and in vivo. The d-galactose-induced malondialdehyde increase was attenuated by CX, as well as the increase in aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, and creatinine level. In addition, the activities of antioxidant enzymes were markedly renewed, and the gene expressions of these enzymes were upregulated in CX groups. The results of histological analysis suggested that CX could effectively attenuate the d-galactose-induced structure damage. Furthermore, results of Western blotting analysis showed that CX significantly inhibited the upregulation of nuclear factor protein expression caused by d-galactose. In conclusion, CX could attenuate the liver and kidney injury in d-galactose-treated mice, and the mechanism might be associated with attenuating oxidative stress and inflammatory response.

Aqueous Extract of Clerodendranthus spicatus Exerts Protective Effect on UV-Induced Photoaged Mice Skin.

Clerodendranthus spicatus (Thunb.) C.Y.Wu (CS) is commonly used to treat kidney diseases in traditional Chinese medicine for its prominent anti-inflammatory effect and nourishing function to kidneys. In this study, aqueous extract of CS was assessed for its protective effect on UV-induced skin damage of mice. The chemical compositions of CS aqueous extract were determined by HPLC-ESI-MS/MS, in which 10 components were identified. During the experimental period, CS (0.9, 1.8, and 3.6 g/mL) was externally applied to shaved dorsal skins of mice prior to UV irradiation, daily for ten weeks. The results presented that CS (3.6 g/mL) apparently improved photodamaged skin appearance such as erythema, edema, and coarseness. The abnormal epidermal thickening was significantly reduced, and the dermal structures became more complete. The underlying protective mechanisms were associated with improving antioxidant enzymes activities including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px), downregulating inflammatory cytokines (IL-1ß, IL-6, TNF-α, COX-2, and PGE2) expressions, recovering collagen density, and reducing matrix metalloproteinases productions. Sun protection factor of CS (3.6 g/mL) was 16.21 ± 0.03. Our findings for the first time demonstrated that CS had therapeutic effect on the photoaged skin. The results indicated that CS is a potential agent for photoprotective cosmetics.

Photo-protective activity of pogostone against UV-induced skin premature aging in mice.

Pogostone, a chemical constituent of patchouli oil, has been confirmed to possess favorable anti-inflammatory property. In the present study, we investigated the possible anti-photoaging potential of pogostone and the underlying mechanism against UV-induced skin damage in mice. The macroscopic and histopathological lesions were significantly ameliorated by pretreatment of pogostone as compared to the VC group. Furthermore, topical application of pogostone markedly increased the activities of the antioxidant enzymes, including catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), and observably decreased malonaldehyde (MDA) level. Analysis of inflammatory cytokines showed obvious down-regulation of tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2) in the pogostone groups. In addition, pogostone pretreatment evidently inhibited the abnormal expression of matrix metalloproteinases (MMP-1 and MMP-3). Taken together, pogostone exhibited prominent photo-protective activity mainly by its antioxidative and anti-inflammatory properties, promising it as an effective alternative pharmaceutical therapy for photoaging.

Antipsychotic polypharmacy and quality of life in patients with schizophrenia treated in primary care in China.

OBJECTIVE: In China, maintenance treatment for clinically stable patients with schizophrenia is usually provided by primary care physicians, but their prescribing patterns have not been studied. This study examined the frequency as well as demographic and clinical correlates of antipsychotic polypharmacy (APP) and its impact on quality of life (QOL) in patients with schizophrenia treated in primary care in China. METHOD: A total of 623 community-dwelling patients from 18 randomly selected primary care services were interviewed. Patients' socio-demographic and clinical characteristics, including number of hospitalizations, antipsychotic drug-induced side effects, and QOL were recorded using a standardized protocol and data collection procedure. RESULTS: The rate of APP prescription was 31% (193/623). Of the patients on APP, 89.6% received 2 antipsychotics, 10.4% received 3 or more antipsychotics. Clozapine (35.6%) was the most commonly prescribed second generation antipsychotic (SGA), while perphenazine (17.8%) was the most commonly prescribed first generation antipsychotic (FGA). Multiple logistic regression analyses revealed that patients on APP were more likely to receive SGAs and anticholinergics, had fewer hospitalizations, younger age of onset, and higher doses of antipsychotics. There were no significant differences between the two groups in any of the QOL domains. CONCLUSIONS: Approximately a third of Chinese patients with schizophrenia in primary care receive APP. Further examination of the rationale and appropriateness of APP and its alternatives is warranted.