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Thymoquinone-loaded lipid vesicles: a promising nanomedicine for psoriasis.

Negi P, Sharma I, Hemrajani C … +4 more , Rathore C, Bisht A, Raza K, Katare OP

BMC Complement Altern Med · 2019 Nov · PMID 31771651 · Full text

BACKGROUND: Psoriasis, a recurrent, chronic inflammatory disorder of skin, is a common problem in middle age and elderly people. Thymoquinone (TQ), a lipid soluble benzoquinone is the major active ingredient of volatile... BACKGROUND: Psoriasis, a recurrent, chronic inflammatory disorder of skin, is a common problem in middle age and elderly people. Thymoquinone (TQ), a lipid soluble benzoquinone is the major active ingredient of volatile oil of Nigella sativa (NS), possesses good anti-psoriatic activity. However, its hydrophobicity, poor aqueous solubility, and photosensitive nature obstructs its development. Therefore, in the present research work, ethosomal vesicles (EVs) loaded with TQ were assessed for its anti-psoriatic potential employing mouse-tail model. METHODS: TQ-loaded EVs were prepared by cold method, and characterized for various essential attributes, viz. particle size, morphology, percent drug entrapment, flexibility, rheological and textural analysis, and skin absorption. The optimized formulation was finally evaluated for anti-psoriatic activity on Swiss albino mice employing mouse-tail model for psoriasis. RESULTS: The spherical shaped vesicles were in the nanosize range, and had high flexibility. The EVs incorporated hydrogel was rheologically acceptable and resulted in substantial TQ retention in the skin layers. The % anti-psoriatic drug activity was observed to be substantially better in the case of TQ-loaded ethosomal gel vis-à-vis plain TQ, NS extract, and marketed formulation. CONCLUSIONS: The promising outcomes of the current studies ratify the superiority of TQ-loaded phospholipid-based vesicular systems for the management of psoriasis over other studied test formulations. This study, thus open promising avenues for topical application of TQ in the form of EV hydrogel.

The ameliorative effect of monotropein, astragalin, and spiraeoside on oxidative stress, endoplasmic reticulum stress, and mitochondrial signaling pathway in varicocelized rats.

Karna KK, Choi BR, You JH … +7 more , Shin YS, Cui WS, Lee SW, Kim JH, Kim CY, Kim HK, Park JK

BMC Complement Altern Med · 2019 Nov · PMID 31771569 · Full text

BACKGROUND: Monotropein, astragalin, and spiraeoside (MAS) are active compounds extracted from medicinal herbs; monotropein from Morinda officinalis How (Rubiaceae), astragalin (kaempferol 3-O-glucoside) from Cuscuta chi... BACKGROUND: Monotropein, astragalin, and spiraeoside (MAS) are active compounds extracted from medicinal herbs; monotropein from Morinda officinalis How (Rubiaceae), astragalin (kaempferol 3-O-glucoside) from Cuscuta chinensis Lamark (Convolvulaceae) and spiraeoside from the outer scales of Allium cepa L. (Liliceae) in a ratio of 6.69:0.41:3.61. Monotropein, astragalin, and spiraeoside are well-known antioxidants, anti-inflammatory, and antinociceptive agents. The current investigation aims to study the molecular mechanism of varicocele-induced male infertility and the underlying pharmacological mechanisms of MAS. METHODS: Four groups were included: control (CTR), MAS 200 group (MAS 200 mg/kg), varicocele group (VC), and VC + MAS 200 group (MAS 200 mg/kg). Sprague-Dawley (SD) rats were treated with 200 mg/kg MAS or vehicle once daily for 28 days. The possible signaling mechanism and effects of MAS were measured via histological staining, immunohistochemistry, western blot, and biochemical assays. RESULTS: Parameters such as sperm motility and count, Johnsen's scores, spermatogenic cell density, serum testosterone, testicular superoxide dismutase (SOD), catalase, glutathione peroxidase (GPx) and expression of the steroidogenic acute regulatory protein (StAR) improved significantly in the VC + MAS 200 group compared with the VC group. MAS treatment of varicocele-induced group significantly decreased the levels of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH), as well as testicular interleukin-6 (IL6), tumor necrosis factor-α (TNF-α), ROS/RNS, and malondialdehyde (MDA). It also decreased the apoptotic index and reduced the expression of endoplasmic reticulum (ER) protein levels (Grp78, p-IRE1α, and p-JNK) and apoptotic markers such as cleaved caspase-3 and Bax/Bcl2 ratio. CONCLUSION: This study suggests that the crosstalk between oxidative stress, ER stress, and mitochondrial pathway mediates varicocele-induced testicular germ cell apoptosis. MAS promotes spermatogenesis in varicocele-induced SD rat, probably by decreasing cytokines (IL-6, TNF-α) levels, regulating abnormal sex hormones, and decreasing oxidative stress, ER stress, and apoptosis.

Evaluation of a mouthrinse containing guava leaf extract as part of comprehensive oral care regimen- a randomized placebo-controlled clinical trial.

Nayak N, Varghese J, Shetty S … +5 more , Bhat V, Durgekar T, Lobo R, Nayak UY, U V

BMC Complement Altern Med · 2019 Nov · PMID 31752836 · Full text

BACKGROUND: The control of biofilm adherence on tooth surface has always been the keystone of periodontal therapeutic systems. However, prevalence of gingivitis suggest inadequacy of self-performed oral hygiene measures... BACKGROUND: The control of biofilm adherence on tooth surface has always been the keystone of periodontal therapeutic systems. However, prevalence of gingivitis suggest inadequacy of self-performed oral hygiene measures and need for adjunctive aid for mechanical plaque control. Oral rinses containing chlorhexidine, has been widely used however, with certain limitations. Herbal products have been used widely reflecting its action as alternative and complementary remedy. Hence, the purpose of the present study was to evaluate the antimicrobial and antioxidant efficacy of a Guava leaf extract based mouthrinse in patients with chronic generalized gingivitis as an adjunct to oral prophylaxis. METHODS: Sixty subjects (n = 20) in compliance with the inclusion criteria were randomly assigned to one of the 3 study groups i.e. Group A- 0.15%Guava mouth rinse, Group B- 0.2% Chlorhexidine (CHX) mouth rinse, Group C- Distilled water (placebo). All the participants received professional oral prophylaxis and were dispensed with experimental mouth rinses and instructed to use for period of 30 days. Clinical parameters such as gingival index, plaque index along with microbial colony forming units using plaque samples and antioxidant levels in saliva were estimated at baseline, 30 and 90 days' time intervals. RESULTS: All 3 groups showed gradual reduction in GI, PI and microbial counts. Considering the mean scores of recorded parameters at the scheduled time intervals, notable changes were observed between chlorhexidine and guava mouth rinse compared to placebo group. Although there was improvement in the antioxidant status in all study participants, yet there was no statistically significant difference observed. CONCLUSION: Guava mouth rinse can be used as an empirical adjunct to professional oral prophylaxis owing to its multifactorial properties and favourable acceptance. However, long term studies need to be conducted to validate its use for an extended period of time. TRIAL REGISTRATION: The clinical trial has been prospectively registered on 17th February 2017 by the Clinical Trials Registry-India (CTRI/2017/02/007898).

Development and validation of traditional & complementary medicine (TCM) scales for nurses: Using structural equation modelling (SEM).

Chang HY, Lo CL, Hung YY

BMC Complement Altern Med · 2019 Nov · PMID 31752832 · Full text

OBJECTIVES: This study aimed to develop and validate scales to assess attitudes towards patient' s use of TCM (APUTCM) and to measure a communicative competence in TCM (CCTCM) among nurses. METHODS: The instrument develo... OBJECTIVES: This study aimed to develop and validate scales to assess attitudes towards patient' s use of TCM (APUTCM) and to measure a communicative competence in TCM (CCTCM) among nurses. METHODS: The instrument development process was conducted from Sep 2013 to Jul 2014, using the following steps: 1) item development; 2) internal review and refinement; 3) face and content validation; 4) instrument administration to a development sample; and 5) evaluation of validity and reliability. A convenience sample was used to recruit registered and advanced practice nurses who worked in different regions throughout Taiwan. A total of 755 respondents completed the online questionnaire. Statistical analyses were performed using the software of SPSS Version 21.0 and Analysis of Moment Structures (AMOS) version 24.0. RESULTS: The scale-level indexes (S-CVI) of content validity for both scales were over 80%. The reliabilities for the 13-item APUTCM scale and for the five-item CCTCM scale were 0.88 and 0.84, respectively. The model suitability for both scales was assessed, and the findings revealed suitable parameters for all indicators: GFI = 0.954, AGFI = 0.932, CFI = 0.959, RMSEA = 0.62, and chi-square/df = 3.891 for APUTCM; and GFI = 0.992, AGFI = 0.969, CFI = 0.992, RMSEA = 0.63, and chi-square/df = 4.04 for CCTCM. The convergent and divergent validity of scores on both scales provided evidence in the expected direction. CONCLUSION: This scale development study provides preliminary evidence that suggests that the 13-item APUTCM and the five-item CCTCM are reliable and valid scales for assessing attitudes toward patient's TCM use and communicative competence in TCM.

Prevalence of and attitudes towards complementary therapy use for weight after breast cancer in Australia: a national survey.

Ee C, Cave AE, Naidoo D … +1 more , Boyages J

BMC Complement Altern Med · 2019 Nov · PMID 31752830 · Full text

BACKGROUND: Weight gain is common after breast cancer (BC) treatment and may increase the risk of disease recurrence. Complementary medicine (CM) use is high amongst BC patients. This paper describes the use of CM from a... BACKGROUND: Weight gain is common after breast cancer (BC) treatment and may increase the risk of disease recurrence. Complementary medicine (CM) use is high amongst BC patients. This paper describes the use of CM from a cross-sectional self-administered survey on prevalence and management of weight after BC. METHODS: Use of CM was assessed using a question modified from the I-CAM Questionnaire. Participants were asked to rate perceived effectiveness, advantages and disadvantages, and which CM they were willing to use for weight management if there was evidence for effectiveness. The survey was emailed to members of the Breast Cancer Network Australia Survey and Review Group, the largest consumer advocacy group in Australia for people with breast cancer. RESULTS: There were a total of 309 responses. Three quarters had used CM in the past 12 months. One third had tried CM for weight loss. Yoga, meditation and pilates were perceived to be effective for weight loss. Perceived advantages of CMs for weight loss were the ability to improve general wellbeing, relaxation, and being non-pharmacological while disadvantages were financial cost, finding a reliable practitioner, and lack of research for effectiveness. Three quarters would be willing to try CM for weight loss if there was evidence for effectiveness, with the most popular CMs being acupuncture, relaxation, yoga, supplements, and meditation. CONCLUSIONS: The high use of CM in this group is consistent with previous research. Our research suggests that BC survivors would use acupuncture, meditation, supplements and yoga for weight loss if supported by scientifically-credible evidence. Research into the effectiveness of these treatments on weight loss after BC is warranted.

The effects of Berberis vulgaris consumption on plasma levels of IGF-1, IGFBPs, PPAR-γ and the expression of angiogenic genes in women with benign breast disease: a randomized controlled clinical trial.

Pirouzpanah S, Asemani S, Shayanfar A … +2 more , Baradaran B, Montazeri V

BMC Complement Altern Med · 2019 Nov · PMID 31752829 · Full text

BACKGROUND: The present study was designed to investigate the effects of Berberis vulgaris (BV) juice consumption on plasma levels of insulin-like growth factor (IGF-1), IGF-binding proteins (IGFBPs), and the expression... BACKGROUND: The present study was designed to investigate the effects of Berberis vulgaris (BV) juice consumption on plasma levels of insulin-like growth factor (IGF-1), IGF-binding proteins (IGFBPs), and the expression of PPAR-γ, VEGF and HIF in women with benign breast disease. METHODS: This parallel design randomized, double-blind controlled clinical trial was conducted on 85 eligible patients diagnosed with benign breast disease. They were assigned randomly into either BV juice group (n = 44, BV juice: 480 ml/day) or placebo group (n = 41, BV placebo juice: 480 ml/day) for 8 weeks intervention. Participants, caregivers and those who assessed laboratory analyses were blinded to the assignments. Plasma levels of biomarkers were measured at baseline and after 8 weeks by ELISA. Quantitative real-time PCR was used to measure the fold change in the expression of each interested gene. RESULTS: The compliance of participants was 95.2% and 40 available subjects analyzed in each group at last. Relative treatment (RT) effects for BV juice caused 16% fall in IGF-1 concentration and 37% reduction in the ratio of IGF-1/1GFBP1. Absolute treatment effect expressed 111 ng/ml increased mean differences of IGFBP-3 between BV group and placebo. Plasma level of PPAR-γ increased in both groups but it was not significant. Fold changes in the expressions of PPAR-γ, VEGF and HIF showed down-regulation in the intervention group compared to placebos (P < 0.05). CONCLUSIONS: The BV juice intervention over 8 weeks was accompanied by acceptable efficacy and decreased plasma IGF-1, and IGF-1/IGFBP-1 ratio partly could be assigned to enhanced IGFBP-1 level in women with BBD. The intervention caused reductions in the expression levels of PPAR, VEGF, and HIF which are remarkable genomic changes to potentially prevent breast tumorigenesis. TRIAL REGISTRATION: IRCT2012110511335N2. Registered 10 July 2013 (retrospectively registered).

Anti-acne vulgaris effect including skin barrier improvement and 5α-reductase inhibition by tellimagrandin I from Carpinus tschonoskii.

Yin J, Hwang IH, Lee MW

BMC Complement Altern Med · 2019 Nov · PMID 31752827 · Full text

BACKGROUND: Carpinus tschonoskii (CT) has been previously studied for various activities in the improvement of skin diseases. In the present study, we examined the in vitro anti-acne vulgaris (AV) effect of CT leaves (CT... BACKGROUND: Carpinus tschonoskii (CT) has been previously studied for various activities in the improvement of skin diseases. In the present study, we examined the in vitro anti-acne vulgaris (AV) effect of CT leaves (CTL) and tellimagrandin I (TI), one of the main ellagitannins from CT, including skin barrier improvement and 5α-reductase inhibitory activity. METHODS: To test the anti-AV activities of CTL and TI, firstly, anti-oxidative and anti-inflammatory activities including DPPH radical scavenging activity, nitric oxide (NO) inhibitory activity, and cytokines [interleukin (IL)-6 and IL-8] were tested. Skin barrier improvement experiments were tested using developing cornified envelope (CE) formation, and filaggrin mRNA expression level was determined by RT-PCR. The 5α-reductase inhibitory activity was determined by measuring the testosterone levels in rat liver microsomes. RESULTS: CTL and TI showed potent anti-oxidative activity and anti-inflammatory activities. Especially, the cytokine production inhibitory activities of TI were found to be similar to the positive control, epigallocatechin gallate (EGCG). CTL and TI enhanced the CE formation and filaggrin mRNA expression levels and showed potent activities compared to that in the positive control, 1.5 mM Ca. In additionally, CTL and TI showed 5α-reductase inhibitory activities in a dose-dependent manner. CONCLUSION: The results showed that CTL and TI inhibit AV endogenous factors such as 5α-reductase and inflammatory cytokines and affect exogenous factors such as developing skin barrier function (CE and filaggrin levels). Therefore, CTL and TI may be plant-derived agent, promising in the treatment of acne vulgaris.

Cartilage protective and anti-analgesic effects of ALM16 on monosodium iodoacetate induced osteoarthritis in rats.

Choi DJ, Choi SI, Choi BR … +3 more , Lee YS, Lee DY, Kim GS

BMC Complement Altern Med · 2019 Nov · PMID 31752825 · Full text

BACKGROUND: Osteoarthritis (OA) is an age-related joint disease with characteristics that involve the progressive degradation of articular cartilage and resulting chronic pain. Previously, we reported that Astragalus mem... BACKGROUND: Osteoarthritis (OA) is an age-related joint disease with characteristics that involve the progressive degradation of articular cartilage and resulting chronic pain. Previously, we reported that Astragalus membranaceus and Lithospermum erythrorhizon showed significant anti-inflammatory and anti-osteoarthritis activities. The objective of this study was to examine the protective effects of ALM16, a new herbal mixture (7:3) of ethanol extracts of A. membranaceus and L. erythrorhizon, against OA in in vitro and in vivo models. METHODS: The levels of matrix metalloproteinase (MMP)-1, -3 and - 13 and glycosaminoglycan (GAG) in interleukin (IL)-1β or ALM16 treated SW1353 cells were determined using an enzyme-linked immunosorbent and quantitative kit, respectively. In vivo, the anti-analgesic and anti-inflammatory activities of ALM16 were assessed via the acetic acid-induced writhing response and in a carrageenan-induced paw edema model in ICR mice, respectively. In addition, the chondroprotective effects of ALM16 were analyzed using a single-intra-articular injection of monosodium iodoacetate (MIA) in the right knee joint of Wister/ST rat. All samples were orally administered daily for 2 weeks starting 1 week after the MIA injection. The paw withdrawal threshold (PWT) in MIA-injected rats was measured by the von Frey test using the up-down method. Histopathological changes of the cartilage in OA rats were analyzed by hematoxylin and eosin (H&E) staining. RESULTS: ALM16 remarkably reduced the GAG degradation and MMP levels in IL-1β treated SW1353 cells. ALM16 markedly decreased the thickness of the paw edema and writhing response in a dose-dependent manner in mice. In the MIA-induced OA rat model, ALM16 significantly reduced the PWT compared to the control group. In particular, from histological observations, ALM16 showed clear improvement of OA lesions, such as the loss of necrotic chondrocytes and cartilage erosion of more than 200 mg/kg b.w., comparable to or better than a positive drug control (JOINS™ 200 mg/kg) in the cartilage of MIA-OA rats. CONCLUSIONS: Our results demonstrate that ALM16 has a strong chondroprotective effect against the OA model in vitro and in vivo, likely attributed to its anti-inflammatory activity and inhibition of MMP production.

Cytotoxic activity of crude extracts from Datura stramonium's fungal endophytes against A549 lung carcinoma and UMG87 glioblastoma cell lines and LC-QTOF-MS/MS based metabolite profiling.

Tapfuma KI, Uche-Okereafor N, Sebola TE … +5 more , Hussan R, Mekuto L, Makatini MM, Green E, Mavumengwana V

BMC Complement Altern Med · 2019 Nov · PMID 31752824 · Full text

BACKGROUND: Endophytic fungi are a proven source of bioactive secondary metabolites that may provide lead compounds for novel drug discovery. In this study, crude extracts from fungal endophytes isolated from Datura stra... BACKGROUND: Endophytic fungi are a proven source of bioactive secondary metabolites that may provide lead compounds for novel drug discovery. In this study, crude extracts from fungal endophytes isolated from Datura stramonium were evaluated for cytotoxic activity on two human cancer cell lines. METHODS: Fungal endophytes were isolated from surface sterilized aerial parts of D. stramonium and identified using molecular, morphological and phylogenetic methods. Ethyl acetate crude extracts from these isolates were evaluated for cytotoxic activity on A549 lung carcinoma and UMG87 glioblastoma cell lines. Metabolite profiling was then performed by liquid chromatography coupled to quadrupole time-of-flight with tandem mass spectrometry (LC-QTOF-MS/MS) for the cytotoxic crude extract. RESULTS: Eleven fungal endophytes were identified from D. stramonium. Significant cytotoxicity was only observed from the crude extract of Alternaria sp. KTDL7 on UMG87 glioblastoma cells (IC = 21.49 μg/ml). Metabolite profiling of this crude extract tentatively revealed the presence of the following secondary metabolites: 1,8-dihydroxynaphthalene (1), anserinone B (2), phelligridin B (3), metacytofilin (4), phomopsidin (5) and vermixocin A (6). Compounds 2 and 3 have been shown to be cytotoxic in literature. CONCLUSION: The findings in this study suggest that the crude extract of Alternaria sp. KTDL7 possesses compound(s) cytotoxic to glioblastoma multiforme cells. Future studies to isolate and characterize the cytotoxic compound(s) from this fungus could result in lead development of a fungal-based drug for glioblastoma multiforme treatment.

Immuno-enhancement effects of Platycodon grandiflorum extracts in splenocytes and a cyclophosphamide-induced immunosuppressed rat model.

Noh EM, Kim JM, Lee HY … +6 more , Song HK, Joung SO, Yang HJ, Kim MJ, Kim KS, Lee YR

BMC Complement Altern Med · 2019 Nov · PMID 31752816 · Full text

BACKGROUND: Platycodon grandiflorum is a flowering plant that is used in traditional medicine for treating pulmonary and respiratory disorders. It exerts various pharmacological effects, including immunomodulatory and an... BACKGROUND: Platycodon grandiflorum is a flowering plant that is used in traditional medicine for treating pulmonary and respiratory disorders. It exerts various pharmacological effects, including immunomodulatory and anti-cancer activities. The purpose of this study was to confirm the in vitro and in vivo immune-enhancing effects of P. grandiflorum extract (PGE) on splenocytes isolated from cyclophosphamide (CP)-induced immunosuppressed rats. METHODS: For in vitro analysis, splenocytes were treated with PGE at various doses along with CP. Cell viability was measured by a WST-1 assay, and NK cell activity and cytotoxic T lymphocyte (CTL) activity was also examined. In addition, immunoglobulin A (IgA), IgG, and cytokine levels were measured. For in vivo analysis, Sprague Dawley rats were treated with various doses of PGE along with CP. Complete blood count (CBC) was performed, and plasma levels of IgA, IgG, TNF-α, IFN-γ, IL-2, and IL-12 were quantified. Additionally, tissue damage was assessed through histological analyses of the thymus and spleen. RESULTS: PGE treatment enhanced cell viability and natural killer cell and cytotoxic T lymphocyte activity, and increased the production of CP-induced inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA) in splenocytes. In addition, in CP-treated rats, PGE treatment induced the recovery of white blood cell, neutrophil, and lymphocyte counts, along with mid-range absolute counts, and increased the serum levels of inflammatory cytokines (TNF-α, IFN-γ, IL-2, and IL-12) and immunoglobulins (IgG and IgA). Moreover, PGE attenuated CP-induced spleen and thymic damage. CONCLUSIONS: Our results confirmed that PGE exerts an immune-enhancing effect both in vitro and in vivo, suggesting that PGE may have applications as a component of immunostimulatory agents or as an ingredient in functional foods.

Standardized ethanol extract, essential oil and zerumbone of Zingiber zerumbet rhizome suppress phagocytic activity of human neutrophils.

Akhtar NMY, Jantan I, Arshad L … +1 more , Haque MA

BMC Complement Altern Med · 2019 Nov · PMID 31752812 · Full text

BACKGROUND: Zingiber zerumbet rhizome and its bioactive metabolites have previously been reported to exhibit innumerable pharmacological properties particularly anti-inflammatory activities. In the present study, the 80%... BACKGROUND: Zingiber zerumbet rhizome and its bioactive metabolites have previously been reported to exhibit innumerable pharmacological properties particularly anti-inflammatory activities. In the present study, the 80% ethanol extract, essential oil and zerumbone of Z. zerumbet rhizomes were explored for their in vitro immunosuppressive properties on chemotaxis, CD11b/CD18 expression, phagocytosis and chemiluminescence of isolated human polymorphonuclear neutrophils (PMNs). METHODS: The extract was analyzed quantitatively by performing a validated reversed phase high performance liquid chromatography (RP-HPLC). Zerumbone was isolated by chromatographic technique while the essential oil was acquired through hydro-distillation of the rhizomes and further analyzed by gas chromatography (GC) and GC-MS. Chemotaxis assay was assessed by using a 24-well cell migration assay kit, while CD18 integrin expression and phagocytic engulfment were measured using flow cytometry. The reactive oxygen species (ROS) production was evaluated by applying lucigenin- and luminol-enhanced chemiluminescence assays. RESULTS: Zerumbone was found to be the most abundant compound in the extract (242.73 mg/g) and the oil (58.44%). Among the samples tested, the oil revealed the highest inhibition on cell migration with an IC value of 3.24 μg/mL. The extract, oil and zerumbone showed moderate inhibition of CD18 integrin expression in a dose-dependent trend. Z. zerumbet extract showed the highest inhibitory effect on phagocytic engulfment with percentage of phagocytizing cells of 55.43% for PMN. Zerumbone exhibited strong inhibitory activity on oxidative burst of zymosan- and PMA-stimulated neutrophils. Zerumbone remarkably inhibited extracellular ROS production in PMNs with an IC value of 17.36 μM which was comparable to that of aspirin. CONCLUSION: The strong inhibition on the phagocytosis of neutrophils by Z. zerumbet extract and its essential oil might be due the presence of its chemical components particularly zerumbone which was capable of impeding phagocytosis at different stages.

Regulatory effect of Garidisan on dysbiosis of the gut microbiota in the mouse model of ulcerative colitis induced by dextran sulfate sodium.

Pei LY, Ke YS, Zhao HH … +7 more , Liu WZ, Wang L, Jia C, Shi MN, Fu QH, Cui J, Li SC

BMC Complement Altern Med · 2019 Nov · PMID 31752807 · Full text

BACKGROUND: Ulcerative colitis (UC) is a modern refractory disease, and its etiology has been difficult to discern. Studies have shown that UC is closely associated with the gut microbiota. Garidisan is composed of wild... BACKGROUND: Ulcerative colitis (UC) is a modern refractory disease, and its etiology has been difficult to discern. Studies have shown that UC is closely associated with the gut microbiota. Garidisan is composed of wild poppy and Artemisia frigida Willd and is commonly used for the treatment of UC in Inner Mongolia, China. In clinical settings, Garidisan has been found to treat UC effectively, with low recurrence. Previous studies have shown that Garidisan has a good therapeutic effect on mice with UC, but the therapeutic mechanism is still unclear. In this study, we investigated the regulatory effect of Garidisan on dysbiosis of the gut microbiota in a UC mouse model and explored the possible mechanism of the therapeutic effect of Garidisan on UC. METHODS: The UC mouse model was established by the dextran sulfate sodium (DSS) circulating free water drinking method, and the luminal contents were sampled under sterile conditions. High-throughput sequencing of the 16S rRNA gene V3 + V4 region of the luminal contents of the control group, model group, and Garidisan group was conducted, and clustering of operational taxonomic units (OTUs) and species annotation were performed. The differences in species composition and microbial community structure between individual groups of samples were analyzed using MetaStat, LefSe, rank sum test, and Bayesian causal network analysis. RESULTS: The UC mouse model was successfully established and the sequencing results were of adequate quality. There were significant differences in the diversity of luminal contents between the control group, model group, and Garidisan group, and the differences between groups were greater than those within any group. The therapeutic effect of Garidisan on UC is attributed to the direct effect on the Lachnospiraceae family of bacteria. CONCLUSION: Garidisan has a good regulatory effect on the gut microbiota, and Lachnospiraceae could be an important direct target of Garidisan for the treatment of UC.

Mulberry leaf reduces inflammation and insulin resistance in type 2 diabetic mice by TLRs and insulin Signalling pathway.

Tian S, Wang M, Liu C … +2 more , Zhao H, Zhao B

BMC Complement Altern Med · 2019 Nov · PMID 31752797 · Full text

BACKGROUND: It has been testified that Diabetes mellitus (DM) has a close association with chronic inflammation and Toll-like Receptors (TLRs), and DM could be prevented by mulberry leaf. Therefore, a hypothesis came int... BACKGROUND: It has been testified that Diabetes mellitus (DM) has a close association with chronic inflammation and Toll-like Receptors (TLRs), and DM could be prevented by mulberry leaf. Therefore, a hypothesis came into being that mulberry leaf could ameliorate proinflammation and insulin resistance (IR) through TLRs and insulin signalling pathways. METHODS: Water extracts of mulberry leaf (WEM) was given to diabetic mice by gavage for 10 weeks, and the diabetic mice was injected with low-dose streptozocin, fed with high-fat and high-sugar diet. Oral glucose tolerance tests (OGTTs) were conducted. At the same time, homeostasis model assessment of insulin (HOMA-IR) and the level of the inflammatory factor, tumour necrosis factor-α (TNF-α) was measured. The expressions of critical nodes of TLRs and insulin signalling pathway were also examined. RESULTS: WEM contributed to a significant decrease in fasting blood glucose, AUC from the investigation of OGTTs and HOMA-IR. The levels of the inflammatory factor, tumour necrosis factor-α (TNF-α) also declined. Moreover, WEM suppressed the expression of TLR2, myeloid differentiation primary-response protein 88 (MyD88), tumour-necrosis-factor receptor-associated factor 6 (TRAF6), nuclear factor kappa B (NF-κB) in the skeletal muscle. WEM could up-regulate the expression of insulin receptor (InsR) and insulin receptor substrate 1 (IRS1), and down-regulate the phosphorylation of IRS1 in adipose tissue. CONCLUSION: Through this study, a conclusion could be made that WEM mitigates hyperglycemia, IR, and inflammation through the interactions among TLR2 signalling pathway, insulin signalling pathway and TNF-α.

Trends in the utilization of acupuncture among children in Taiwan from 2002 to 2011: a nationwide population-based study.

Wang C, Lee YC, Wu MY … +4 more , Lin CL, Sun MF, Lin JG, Yen HR

BMC Complement Altern Med · 2019 Nov · PMID 31752791 · Full text

BACKGROUND: In recent years, acupuncture has been increasingly integrated into pediatric care worldwide. However, recent epidemiological studies about pediatric users of acupuncture are lacking. The current study aimed t... BACKGROUND: In recent years, acupuncture has been increasingly integrated into pediatric care worldwide. However, recent epidemiological studies about pediatric users of acupuncture are lacking. The current study aimed to fill the gap and carry out the large-scale investigation on the basis of the pediatric population in Taiwan. METHODS: We conducted a nationwide population-based study to investigate the utilization of acupuncture in Taiwan. We analyzed data from the Longitudinal Health Insurance Database 2000 (LHID 2000). The datasets contained all original claims data for 1 million beneficiaries who were randomly sampled from the registry of all beneficiaries enrolled in the Taiwan's National Health Insurance Program from January 1, 2000 to December 31, 2011. Children younger than 18 years old were enrolled into our study for analysis. The demographic data, treatment modalities and distributions by disease categories of the pediatric acupuncture users were analyzed by descriptive statistics. Logistic regression analysis was used to investigate the trends in acupuncture use over time. RESULTS: The one-year prevalence of pediatric acupuncture users increased from 1.78% in 2002 to 5.34% in 2011. Acupuncture use significantly increased each year (p-value< 0.0001). Patients who were male, of greater age, resided in highly urbanized areas and suffered from injury or disorders of the musculoskeletal system were more likely to accept acupuncture treatment. Infantile cerebral palsy and psychoses were the top two health issues among those receiving complex acupuncture treatment. Older (> 9 years old) children tended to receive acupuncture treatment due to injury and musculoskeletal system disorders more than younger (≤9 years old) children. CONCLUSIONS: Our study revealed that the utilization of acupuncture in pediatrics became increasingly popular year by year in Taiwan from 2002 to 2011. The results of this study may provide some valuable information for further clinical practice and acupuncture research, as well as to the government and societies concerning pediatric health care.

Qingkailing injection ameliorates cerebral ischemia-reperfusion injury and modulates the AMPK/NLRP3 Inflammasome Signalling pathway.

Ma C, Wang X, Xu T … +9 more , Yu X, Zhang S, Liu S, Gao Y, Fan S, Li C, Zhai C, Cheng F, Wang Q

BMC Complement Altern Med · 2019 Nov · PMID 31747940 · Full text

BACKGROUND: Cerebral ischemia is the second-leading cause of death and the main cause of permanent adult disabilities worldwide. Qingkailing (QKL) injection, a patented Chinese medicine approved by the China Food and Dru... BACKGROUND: Cerebral ischemia is the second-leading cause of death and the main cause of permanent adult disabilities worldwide. Qingkailing (QKL) injection, a patented Chinese medicine approved by the China Food and Drug Administration, has been widely used in clinical practice to treat cerebral ischemia in China. The NOD-like receptor pyrin 3 (NLRP3) inflammasome is activated in cerebral ischemia and thus, is an effective therapeutic target. AMP-activated protein kinase (AMPK) is an important regulator inhibiting NLRP3 inflammasome activation. METHODS: We investigated the potential of QKL injection to provide neuroprotection after cerebral ischemia in a rat model of middle cerebral artery occlusion (MCAO). Adult male Sprague-Dawley rats (210-230 g) were randomly divided into three groups which consist of sham, MCAO and 3 ml/kg QKL. Rats in the QKL group received intraperitoneal injections of 3 ml/kg QKL, while rats in other groups were given saline in the same volumes. After 90 min ischemia and 24 h reperfusion, neurological function, laser speckle imaging, brain infarction, brain water content and brain blood barrier permeability were examined and cell apoptosis at prefrontal cortex were evaluated 24 h after MCAO, and western blot and real-time quantitative polymerase chain reaction was also researched, respectively. RESULTS: Intraperitoneal administration of QKL alleviated neurological deficiencies, cerebral infarction, blood-brain barrier permeability, brain oedema and brain cell apoptosis after MCAO induction. QKL decreased pro-inflammatory cytokines, TNF-α, IL-6 and IL-1β, and increased anti-inflammatory cytokines, IL-4 and IL-10. Furthermore, QKL activated phosphorylated AMPK, decreased oxidative stress and decreased NLRP3 inflammasome activation. CONCLUSIONS: QKL relieved cerebral ischemia reperfusion injury and suppressed the inflammatory response by inhibiting AMPK-mediated activation of the NLRP3 inflammasome. These results suggest that QKL might have potential in treating brain inflammatory response and attenuating the cerebral ischemia-reperfusion injury.

Inhibitory effects of ChondroT and its constituent herbs on RANKL-induced osteoclastogenesis.

Guo RH, Kim SJ, Choi CH … +3 more , Na CS, Kang BY, Kim YR

BMC Complement Altern Med · 2019 Nov · PMID 31747910 · Full text

BACKGROUND: ChondroT is a complex herbal medicine consisting of water extracts of Ostericum koreanum (Maxim.) Kitag., Lonicera japonica Thunb., Angelica gigas Nakai, Clematis manshurica Rupr., and Phellodendron amurense... BACKGROUND: ChondroT is a complex herbal medicine consisting of water extracts of Ostericum koreanum (Maxim.) Kitag., Lonicera japonica Thunb., Angelica gigas Nakai, Clematis manshurica Rupr., and Phellodendron amurense Rupr. (6:4:4:4:3). Previous studies have reported that ChondroT possesses chondroprotective and anti-inflammatory, anti-osteoarthritic, and anti-hyperuricemic activities. The study is aim to demonstrate the effects of ChondroT and its five constituent herbs on receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and the underlying mechanisms. METHODS: Osteoclastogenesis was identified in bone marrow-derived macrophages (BMDMs) by tartrate-resistant acid phosphatase (TRAP) staining assay, actin ring formation assay and the bone resorption assay. For the molecular mechanisms, activation of RANKL-induced NF-κB and MAPK signaling pathways and the expression levels of osteoclast-specific proteins were investigated by Western blotting. Cell viability was assessed by MTT assay. Actin ring formation and NF-κB translocation were evaluated by immunostaining. RESULTS: ChondroT and each of its constituent herbs significantly suppressed osteoclast differentiation dose dependently, and decreased actin ring formation as well as bone-resorbing capacity. Mechanistically, ChondroT and its constituent herbs downregulated the expressional levels of osteoclast-specific proteins such as NFATc1, c-Fos, Cathepsin K, and matrix metalloproteinase 9 (MMP9) by suppressing NF-κB translocation to nucleus and MAPKs phosphorylation at different levels. Compared to its five constituent herbs, ChondroT exhibited the best inhibitory efficiency against osteoclastogenesis. CONCLUSIONS: Taken together, ChondroT has anti-osteoclastogenesis properties by inhibiting NF-κB and MAPKs pathways. It could be considered as a potential therapeutic candidate for the treatment of osteoclast-related bone diseases.

Protective effect of Shenmai injection on doxorubicin-induced cardiotoxicity via regulation of inflammatory mediators.

Zhang S, You ZQ, Yang L … +4 more , Li LL, Wu YP, Gu LQ, Xin YF

BMC Complement Altern Med · 2019 Nov · PMID 31744501 · Full text

BACKGROUND: Doxorubicin (DOX) is a chemotherapy drug for malignant tumors. The clinical application of DOX is limited due to its dosage relative cardiotoxicity. Oxidative damage and cardiac inflammation appear to be invo... BACKGROUND: Doxorubicin (DOX) is a chemotherapy drug for malignant tumors. The clinical application of DOX is limited due to its dosage relative cardiotoxicity. Oxidative damage and cardiac inflammation appear to be involved in DOX-related cardiotoxicity. Shenmai injection (SMI), which mainly consists of Panax ginsengC.A.Mey.and Ophiopogon japonicus (Thunb.) Ker Gawl, is widely used for the treatment of atherosclerotic coronary heart disease and viral myocarditis in China. In this study, we investigated the protective effect of Shenmai injection on doxorubicin-induced acute cardiac injury via the regulation of inflammatory mediators. METHODS: Male ICR mice were randomly divided into seven groups: control, DOX (10 mg/kg), SMI (5 g/kg), DOX with pretreatment with SMI (0.5 g/kg, 1.5 g/kg or 5 g/kg) and DOX with post-treatment with SMI (5 g/kg). Forty-eight hours after the last DOX administration, all mice were anesthetized for ultrasound echocardiography. Then, serum was collected for biochemical and inflammatory cytokine detection, and heart tissue was collected for histological and Western blot detection. RESULTS: A cumulative dose of DOX (10 mg/kg) induced acute cardiotoxicity in mice manifested by altered echocardiographic outcome, and increased tumor necrosis factor, interleukin 6 (IL-6), monocyte chemotactic protein 1, interferon-γ, and serum AST and LDH levels, as well as cardiac cytoplasmic vacuolation and myofibrillar disarrangement. DOX also caused the increase in the expression of IKK-α and iNOS and produced a large amount of NO, resulting in the accumulation of nitrotyrosine in the heart tissue. Pretreatment with SMI elicited a dose-dependent cardioprotective effect in DOX-dosed mice as evidenced by the normalization of serum inflammatory mediators, as well as improve dcardiac function and myofibril disarrangement. CONCLUSIONS: SMI could recover inflammatory cytokine levels and suppress the expression of IKK-α and iNOS in vivo, which was increased by DOX. Overall, there was evidence that SMI could ameliorate DOX-induced cardiotoxicity by inhibiting inflammation and recovering heart dysfunction.

Antibacterial activities, proposed mode of action and cytotoxicity of leaf extracts from Triumfetta welwitschii against Pseudomonas aeruginosa.

Mombeshora M, Mukanganyama S

BMC Complement Altern Med · 2019 Nov · PMID 31744500 · Full text

BACKGROUND: Pseudomonas aeruginosa has become a main cause of Gram-negative infection, particularly in patients with compromised immunity. High rates of resistance to antibiotics are associated with nosocomial infections... BACKGROUND: Pseudomonas aeruginosa has become a main cause of Gram-negative infection, particularly in patients with compromised immunity. High rates of resistance to antibiotics are associated with nosocomial infections caused by P. aeruginosa strains. The search for novel antimicrobials has been necessitated by the emergence of antimicrobial resistance in some bacteria Plant-based antimicrobials has great potential to combat microbial infections using a variety of mechanisms. Triumfetta welwitschii plant roots are traditionally used to treat symptoms of diarrhoea and fever, suggesting that it possess antimicrobial and immunomodulatory effects. Since research investigating antimicrobial properties of the roots of Triumfetta welwitschii has been explored, there is need to investigate the antimicrobial activity of its leaf extracts in order to probe their prospective use as new antimicrobial agents that can be used to combat nosocomial infections. The objective of this study was to evaluate the antibacterial activities, the mode of action and cytotoxicity of T. welwitschii leaf extracts. METHOD: Extracts of T. welwitschii leaves were obtained using eight different solvents, the serial exhaustive extraction method and the cold maceration technique. In vitro antibacterial activity evaluation of the extracts was done on eight bacterial isolates using the broth microdilution method. The mode of action for the most potent extracts was investigated using the rhodamine 6G efflux assay and the propidium iodide-based membrane damage assay. Toxicity of the extracts was evaluated using the haemolytic and MTT (3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide) assays. RESULTS: The results showed that acetone, ethanol and dichlorometane: methanol extracts had the most potent antibacterial activities against Pseudomonas aeruginosa (ATCC 27853). All three extracts caused membrane disruption of P. aeruginosa as shown by nucleic acid leakage. All three extracts were unable to inhibit efflux pumps. CONCLUSION: The presence of antibacterial activities and low toxicity shown by the extracts indicates that the plant may be a source of effective antibacterial against some bacterial infections caused by P. aeruginosa. The disruption of membrane integrity is one possible mode of action of antibacterial activity of the potent extracts.

Inhibitory effects of berberine on proinflammatory M1 macrophage polarization through interfering with the interaction between TLR4 and MyD88.

Gong J, Li J, Dong H … +11 more , Chen G, Qin X, Hu M, Yuan F, Fang K, Wang D, Jiang S, Zhao Y, Huang W, Huang Z, Lu F

BMC Complement Altern Med · 2019 Nov · PMID 31744490 · Full text

BACKGROUNDS: Inflammation is recognized as the key pathological mechanism of type 2 diabetes. The hypoglyceamic effects of berberine (BBR) are related to the inhibition of the inflammatory response, but the mechanism is... BACKGROUNDS: Inflammation is recognized as the key pathological mechanism of type 2 diabetes. The hypoglyceamic effects of berberine (BBR) are related to the inhibition of the inflammatory response, but the mechanism is not completely clear. METHODS: The inflammatory polarization of Raw264.7 cells and primary peritoneal macrophages were induced by LPS, and then effects and underlying mechanisms of BBR were explored. An inflammatory model was established by LPS treatment at different concentrations for different treatment time. An ELISA assay was used to detect the secretions of TNF-α. RT-PCR was applied to detect M1 inflammatory factors. The F4/80 ratio and CD11c ratio of primary peritoneal macrophages were determined by flow cytometry. The expressions of p-AMPK and TLR4 were detected by Western blot. The cytoplasmic and nuclear distributions of NFκB p65 were observed by confocal microscopy. The binding of TLR4 to MyD88 was tested by CoIP, and the affinity of BBR for TLR4 was assessed by molecular docking. RESULTS: Upon exposure to LPS, the secretion of TNF-α and transcription of inflammatory factors in macrophages increased, cell morphology changed and protrusions appeared gradually, the proportion of F4/80CD11c M1 macrophages increased, and the nuclear distribution of NFκB p65 increased. BBR pretreatment partially inhibited the changes mentioned above. However, the expression of TLR4 and p-AMPK did not change significantly after LPS intervention for 3 h. Meanwhile, CoIP showed that the interaction between TLR4 and MyD88 increased, and BBR inhibited the binding. Molecular docking suggested that BBR might interact with TLR4. CONCLUSIONS: Inflammatory changes were induced in macrophages after LPS stimulation for 3 h, and BBR pretreatment inhibited inflammatory polarization. BBR might interact with TLR4 and disturb TLR4/MyD88/NFκB signalling pathway, and it might be the mechanism by which BBR attenuated inflammation in the early phase.

Weipiling ameliorates gastric precancerous lesions in Atp4a mice.

Liu W, Zhao ZM, Liu YL … +2 more , Pan HF, Lin LZ

BMC Complement Altern Med · 2019 Nov · PMID 31744486 · Full text

BACKGROUND: Altered cellular metabolism is considered to be one of the hallmarks of cancer (Coller, Am J Pathol 184:4-17, 2014; Kim and Bae, Curr Opin Hematol 25:52-59, 2018). However, few studies have investigated the r... BACKGROUND: Altered cellular metabolism is considered to be one of the hallmarks of cancer (Coller, Am J Pathol 184:4-17, 2014; Kim and Bae, Curr Opin Hematol 25:52-59, 2018). However, few studies have investigated the role of metabolism in the development of gastric precancerous lesions (GPLs). Weipiling (WPL), a traditional Chinese medicine formula for treatment of GPLs. In this study, we evaluated the amelioration of GPLs by WPL and investigated the possible role of WPL in regulating glucose metabolism. METHODS: Firstly, the major components of WPL are chemically characterized by HPLC analytical method. In this study, we chose the Atp4a mouse model (Spicer etal., J Biol Chem 275:21555-21565, 2000) for GPL analysis. Different doses of WPL were administered orally to mice for 10 weeks. Next, the pathological changes of gastric mucosa were assessed by the H&E staining and AB-PAS staining. In addition, TUNEL staining was used to evaluate apoptosis, and we further used immunohistochemically labelled CDX2, MUC2, ki-67, PTEN, and p53 proteins to assess the characteristic changes of gastric mucosa in precancerous lesions. The levels of such transporters as HK-II, PKM2, ENO1, MPC1, and LDHA were determined by Western blot analysis. Finally, we assessed the expression of mTOR, HIF-1α, AMPK, Rheb, TSC1 and TSC2 protein in the gastric mucosa of Atp4amice. RESULTS: In this work, we evaluated the protective effect of WPL on gastric mucosa in mice with precancerous lesions. The aberrant apoptosis in gastric mucosa of gastric pre-cancerous lesions was controlled by WPL (P<0.05). Furthermore, WPL suppressed the expression of CDX2, MUC2, ki-67, PTEN and p53, as the levels of these proteins decreased significantly compared with the model group (P<0.05). In parallel, WPL significantly suppressed the expression of transporters, such as HK-II, PKM2, ENO1, MPC1 and LDHA (P<0.05). In addition, mTOR, HIF-1a, AMPK, Rheb, TSC1 and TSC2 protein levels in gastric mucosa of Atp4a mice in the high- and low-dose WPL groups were significantly lower than those in the model group (P<0.05), while the expression of TSC1 and TSC2 protein was significantly higher (P<0.05). CONCLUSIONS: Conclusively, WPL could ameliorate GPLs in Atp4a mice by inhibiting the expression of transporters and suppressing the aberrant activation of mTOR/HIF-1α.
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