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Topical hydrogel containing Fumaria vaillantii Loisel. extract enhances wound healing in rats.

Davoodi-Roodbordeii F, Afshar M, Haji Abas Tabrizi F … +4 more , Choopani S, Torkaman G, Moayer F, Salimi M

BMC Complement Altern Med · 2019 Sep · PMID 31511001 · Full text

BACKGROUND: Fumaria species (Fumariacea) has traditionally been used in wound healing in Iranian folk medicine. However, with the discovery of newer agents, its use has faded off into total obscurity. This study explored... BACKGROUND: Fumaria species (Fumariacea) has traditionally been used in wound healing in Iranian folk medicine. However, with the discovery of newer agents, its use has faded off into total obscurity. This study explored the wound healing potential of a gel containing 10% Fumaria vaillantii Loisel through topical application of total extract in a model of excisional as well as incisional wound healing in albino Wistar rats. METHODS: Rats were anesthetized, and excisional skin wound was established using a sterilized surgical scissors. The animals were then treated with 10% F.vaillantii topical gel formulation along with the gel base. The treatments were administered once a day after the injury for 21 days. For topical treatment, the hydrogel was formulated and evaluated for chemical and physical characteristics. Histopathological analysis with hematoxylin and eosin (H&E) was used for microscopic examination of the skin tissues on 21-day-old sections of excision wound. To verify collagen formation, hydroxyproline determination was performed 21 days post wound healing. Breaking strength was determined in a 10-day-old incision wound by the uniaxial tensile test. RESULTS: Topical administration of F.vaillantii gel formulation significantly enhanced skin wound closure on the 6th post-wounding day compared to both gel base and the negative control, indicating an accelerated wound healing process, while a significant difference was observed on 10th and 14th post -wound days in F.vaillantii treatment compared to the negative control groups. Gel formulation prepared with a 10% F. vaillantii extract exhibited a response in terms of wound epithelialization, angiogenesis and number of hair follicles at wound area better than the gel base on the 21st post-wound day. Application of gel base produced further advantages by increasing hydroxyproline content and collagen fiber thickness. Our results on incision wound model were supported by histopathological data indicating the role of gel base in the enhancement of breaking strength. CONCLUSION: Traditional use of Fumaria species in the skin diseases was justified in this study by revealing the increase in wound healing activity after hydrogel containing F. vaillantii total extract administration.

Investigation of Brassica juncea, Forsythia suspensa, and Inula britannica: phytochemical properties, antiviral effects, and safety.

Bae WY, Kim HY, Choi KS … +5 more , Chang KH, Hong YH, Eun J, Lee NK, Paik HD

BMC Complement Altern Med · 2019 Sep · PMID 31510997 · Full text

BACKGROUND: General antiviral agents such as oseltamivir are associated with certain adverse effects and the emergence of resistance. This study investigated the phytochemical properties, antiviral activities, and safety... BACKGROUND: General antiviral agents such as oseltamivir are associated with certain adverse effects and the emergence of resistance. This study investigated the phytochemical properties, antiviral activities, and safety of three herbs used in traditional Korean medicine. METHODS: Extracts of three medicinal herbs (Brassica juncea, Forsythia suspensa, and Inula britannica) were prepared using ethanol or water. The total phenolic, flavonoid, and saponin content, condensed tannin content, and reducing sugar content of the herb extracts were determined via phytochemical screening. Tandem mass analysis was performed using an ultra-performance liquid chromatography (UPLC)-electrospray ionization (ESI)-Q/Orbitrap instrument. Virus titrations were determined via tissue culture infective dose (TCID) and cytotoxicity assays. Hemolysis and hepatotoxicity were measured to determine safety. RESULTS: Among the three medicinal herbs, F. suspensa showed the highest concentration of phenolic compounds, flavonoids, and saponins. The number of phytochemical compounds detected via tandem mass analysis of B. juncea, F. suspensa, and I. britannica was 5 (including sinigrin, m/z [M-H] = 358.02), 14 (including forsythoside A, m/z [M-H] = 623.19), and 18 (including chlorogenic acid, m/z [M-H] = 353.20), respectively. The antiviral effects of the B. juncea extracts (ethanol and water) and I. britannica extract (ethanol) were further investigated. The ethanol extract of B. juncea showed a 3 Log TCID/25 μL virus titration reduction and the water extract showed a selectivity index of 13.668 against infected influenza H1N1 virus A/NWS/33. The B. juncea extracts did not show hemolysis activities and hepatotoxicity (< 20%). The ethanol extract of I. britannica showed the most effective virus titration decrease, whereas its hemolytic and hepatotoxicity values were the most significantly different compared to the control. Despite the high concentration of phytochemicals detected in F. suspensa, the extract showed approximately 1 Log TCID/25 μL at the highest concentration. CONCLUSION: B. juncea may show antiviral effects against H1N1 in a host. In addition, B. juncea may also show decreased disadvantages compared to other antiviral agents.

A biological extract of turmeric (Curcuma longa) modulates response of cartilage explants to lipopolysaccharide.

Pearson W, Kott LS

BMC Complement Altern Med · 2019 Sep · PMID 31506082 · Full text

BACKGROUND: Turmeric is commonly used as a dietary treatment for inflammation, but few studies have evaluated the direct effect of turmeric on cartilage. The purpose of this study was to characterize cartilage explants'... BACKGROUND: Turmeric is commonly used as a dietary treatment for inflammation, but few studies have evaluated the direct effect of turmeric on cartilage. The purpose of this study was to characterize cartilage explants' inflammatory responses to lipopolysaccharide in the presence of a simulated biological extract of turmeric. METHODS: Turmeric was incubated in simulated gastric and intestinal fluid, followed by inclusion of liver microsomes and NADPH. The resulting extract (TUR) was used to condition cartilage explants in the presence or absence of lipopolysaccharide. Explants were cultured for 96 h (h); the first 24 h in basal tissue culture media and the remaining 72 h in basal tissue culture media containing TUR (0, 3, 9 or 15 μg/mL). Lipopolysaccharide (0 or 5 μg/mL) was added for the final 48 H. media samples were collected immediately prior to lipopolysaccharide exposure (0 h) and then at 24 and 48 h after, and analyzed for prostaglandin E (PGE), glycosaminoglycan (GAG), and nitric oxide (NO). Explants were stained with calcein-AM for an estimate of live cells. Data were analyzed using a 2-way repeated measures (GAG, PGE, NO) or 1-way ANOVA without repeated measures (viability). Significance accepted at p < 0.05. RESULTS: TUR significantly reduced PGE NO and GAG, and calcein fluorescence was reduced. CONCLUSIONS: These data contribute to the growing body of evidence for the utility of turmeric as an intervention for cartilage inflammation.

Parental satisfaction and perception of Progress in influencing the Practice of complementary health approaches in children with autism: a cross sectional survey from Negeri Sembilan, Malaysia.

Ong JJ

BMC Complement Altern Med · 2019 Sep · PMID 31500611 · Full text

BACKGROUND: Parents' use of complementary health approaches (CHA) for children with autism spectrum disorder (ASD) are common despite the uncertain evidence of its benefit. Parents often adopt CHA due to dissatisfaction... BACKGROUND: Parents' use of complementary health approaches (CHA) for children with autism spectrum disorder (ASD) are common despite the uncertain evidence of its benefit. Parents often adopt CHA due to dissatisfaction with conventional treatment. This study aimed to examine parents' satisfaction with ASD treatment and their perception of progress in their child's development. Parents' use of CHA among children with ASD and the factors related were also evaluated. METHODS: Self-administered questionnaires were completed by 48 parents of children with ASD at a single tertiary referral hospital in Malaysia. Correlation analysis was used to explore associations between parental satisfaction scores, perception of progress scores and use of CHA. RESULTS: Use of CHA was reported by parents for 35.4% of children with ASD in the sample. Parents who were less satisfied with conventional treatment and parents who perceived poorer progress in their child's development were more likely to use CHA. Strong positive relationship was found between parent satisfaction with ASD treatment scores and parent perception of progress scores, which indicates that parents who were satisfied with treatment were more likely to perceive greater progress in their child's development. Improvement in child's progress was most appreciated by parents in their child's behavior (85.5%), social skills (83.3%) and motor skills (77.1%). CONCLUSION: The use of CHA was common among children with ASD. Parents were more likely to practice CHA when they were less satisfied with conventional treatment and perceived poorer progress. A larger multicenter study is required to further explore the practice of CHA among children with ASD throughout Malaysia.

The impact of uncertainty in society on the use of traditional, complementary and alternative medicine: a comparative study on visits to alternative/traditional/folk health care practitioners.

Misawa J, Ichikawa R, Shibuya A … +4 more , Maeda Y, Arai I, Hishiki T, Kondo Y

BMC Complement Altern Med · 2019 Sep · PMID 31500604 · Full text

BACKGROUND: While traditional, complementary and alternative medicine (TCAM) is gaining increased interest worldwide, the structural factors associated with the usage of TCAM at the social level have not been sufficientl... BACKGROUND: While traditional, complementary and alternative medicine (TCAM) is gaining increased interest worldwide, the structural factors associated with the usage of TCAM at the social level have not been sufficiently explored. We aim to understand the social structure of uncertainty in society that affects the TCAM usage for men and women. METHODS: We studied 32 countries using data from the International Social Survey Programme and the World Bank. In this study, we defined TCAM usage as visits to an alternative/traditional/folk health care practitioner during the past 12 months. We performed a correlation analysis and used a generalized linear model . RESULTS: The prevalence of TCAM usage in terms of visits to practitioners was 26.1% globally, while usage varied across the 32 countries. Generalized linear models showed that unemployment rate was associated with the prevalence of TCAM usage in terms of visits to practitioners. CONCLUSIONS: At the social-structural level TCAM usage involving visits to practitioners was related to job insecurity. Job insecurity led to a decrease in TCAM usage regarding visits to practitioners. These findings suggest that it is necessary to consider the social-structural factors of uncertainty in society when designing health policies related to TCAM.

Evaluation of antimicrobial activity of chondrillasterol isolated from Vernonia adoensis (Asteraceae).

Mozirandi W, Tagwireyi D, Mukanganyama S

BMC Complement Altern Med · 2019 Sep · PMID 31492140 · Full text

BACKGROUND: Bacteria have developed resistance to most of the current antibiotics. There is evidence suggesting that plant-derived compounds have a potential for interacting with biological processes. One of the plants c... BACKGROUND: Bacteria have developed resistance to most of the current antibiotics. There is evidence suggesting that plant-derived compounds have a potential for interacting with biological processes. One of the plants commonly used in African ethnomedicine is Vernonia adoensis from the Asteraceae family. The leaves of the plant have been reported to have antimicrobial activity. Hence, the aim of this study was to isolate the bioactive compounds from the leaf extract and evaluate their antibacterial activity on Staphylococcus aureus, Klebsiella pneumoniae and Pseudomonas aeruginosa. In addition, the effect of the isolated compound on biofilms of P. aeruginosa was determined. METHODS: Isolation of phytochemicals from the leaves of V. adoensis was done using column chromatography. Preparative TLC was used to further isolate mixed compounds in the fractions. Nuclear magnetic resonance spectroscopy and mass spectrometry was used to identify the isolated pure compounds. The broth microdilution assay was carried out to evaluate the antibacterial activity of the isolated compound on P. aeruginosa, S. aureus and K. pneumoniae. Crystal violet staining technique was used to evaluate the effect of the isolated compound on biofilms of P. aeruginosa. RESULTS: The compound isolated from V. adoensis was identified as chondrillasterol. Chondrillasterol exhibited 25, 38 and 65% inhibition of growth on S. aureus, K. pneumoniae and P. aeruginosa respectively. At 1.6 μg/mL chondrillasterol completely disrupted mature biofilm of P. aeruginosa while at 100 μg/mL the compound completely inhibited formation of biofilms of the bacteria. CONCLUSION: Chondrillasterol isolated from V. adoensis has antibacterial properties against S. aureus, K. pneumoniae and P. aeruginosa. The compound also has biofilm inhibition and disruption activity against P. aeruginosa biofilms. Thus, the active phytochemical could be a useful template for the development of new antimicrobial agents with both antibacterial and antibiofilm activity.

Cyanidin-3-rutinoside acts as a natural inhibitor of intestinal lipid digestion and absorption.

Thilavech T, Adisakwattana S

BMC Complement Altern Med · 2019 Sep · PMID 31488210 · Full text

BACKGROUND: Cyanidin-3-rutinoside (C3R), a naturally occurring anthocyanin, possesses anti-oxidant, anti-hyperglycemic, anti-glycation and cardioprotective properties. However, its mechanisms responsible for anti-hyperli... BACKGROUND: Cyanidin-3-rutinoside (C3R), a naturally occurring anthocyanin, possesses anti-oxidant, anti-hyperglycemic, anti-glycation and cardioprotective properties. However, its mechanisms responsible for anti-hyperlipidemic activity have not been fully identified. The aim of the study was to investigate the lipid-lowering mechanisms of C3R through inhibition of lipid digestion and absorption in vitro. METHODS: The inhibitory activity of C3R against pancreatic lipase and cholesterol esterase was evaluated using enzymatic fluorometric and enzymatic colorimetric assays, respectively. An enzyme kinetic study using Michaelis-Menten and the derived Lineweaver-Burk plot was performed to understand the possible types of inhibition. The formation of cholesterol micelles was determined using the cholesterol assay kit. The bile acid binding was measured using the colorimetric assay. The NBD cholesterol uptake in Caco-2 cells was determined using fluorometric assay. The mRNA expression of cholesterol transporter (Niemann-Pick C1-like 1) was determined by RT-PCR. RESULTS: The results showed that C3R was a mixed-type competitive inhibitor of pancreatic lipase with the IC value of 59.4 ± 1.41 μM. Furthermore, C3R (0.125-1 mM) inhibited pancreatic cholesterol esterase about 5-18%. In addition, C3R inhibited the formation of cholesterol micelles and bound to primary and secondary bile acid. In Caco-2 cells, C3R (12.5-100 μM) exhibited a significant reduction in cholesterol uptake in both free cholesterol (17-41%) and mixed micelles (20-30%). Finally, C3R (100 μM) was able to suppress mRNA expression of NPC1L1 in Caco-2 cells after 24 h incubation. CONCLUSIONS: The present findings suggest that C3R acts as a lipid-lowering agent through inhibition of lipid digestion and absorption.

Anti-obesity effect of Yangkyuksanwha-tang in high-fat diet-induced obese mice.

Koh YM, Jang SW, Ahn TW

BMC Complement Altern Med · 2019 Sep · PMID 31488172 · Full text

BACKGROUND: Yangkyuksanwha-tang (YST) is an herbal medicine based on Sasang constitutional medicine (SCM) and is widely used in Korean traditional medicine. The aim of the study was to evaluate the effect of YST on obesi... BACKGROUND: Yangkyuksanwha-tang (YST) is an herbal medicine based on Sasang constitutional medicine (SCM) and is widely used in Korean traditional medicine. The aim of the study was to evaluate the effect of YST on obesity in high-fat diet (HFD)-induced obese mice. METHODS: We induced obesity in C57bl/6 J mice using a HFD, and then orally administered 300 mg/kg YST for 6 weeks. We measured body weight, food efficiency, organ and fat weight, serum biochemical parameters, and obesity-related gene expression, and carried out histological analysis at the end of the experimental period. RESULTS: YST significantly reduced the absolute body weight and food efficiency ratio. The serum, aminotransferase, glucose, total cholesterol, triglyceride, and low-density lipoprotein-cholesterol levels were significantly lower in the YST-treated group than in the control group, whereas the high-density lipoprotein-cholesterol level in the YST-treated group was significantly higher. The YST-treated group also showed a significant reduction in regional fatty tissues and the absolute weight of various organs. We also observed a significantly reduced expression of AP2/FABP4, C/EBP-β, leptin, and SREBP1c/ADD1 mRNA, and significantly increased expression of UCP-2 and adiponectin mRNA in adipose tissue in the YST-treated group. YST also decreased the lipid droplet size and lipid accumulation in the liver, as well as adipocyte size in epididymal adipose tissue. At the dose tested, YST was non-toxic to the liver and kidneys of the mice. CONCLUSION: The results imply that YST has anti-obesity effects in obesity-induced mice. Although the number of experimental animals was limited and the drug effects concern mice, rather than humans, which have different constitutions, the study has valuable implications with respect to the general effects of YST.

Variation in the metabolites and α-glucosidase inhibitory activity of Cosmos caudatus at different growth stages.

Wan-Nadilah WA, Akhtar MT, Shaari K … +3 more , Khatib A, Hamid AA, Hamid M

BMC Complement Altern Med · 2019 Sep · PMID 31488132 · Full text

BACKGROUND: Cosmos caudatus is an annual plant known for its medicinal value in treating several health conditions, such as high blood pressure, arthritis, and diabetes mellitus. The α-glucosidase inhibitory activity and... BACKGROUND: Cosmos caudatus is an annual plant known for its medicinal value in treating several health conditions, such as high blood pressure, arthritis, and diabetes mellitus. The α-glucosidase inhibitory activity and total phenolic content of the leaf aqueous ethanolic extracts of the plant at different growth stages (6, 8. 10, 12 and 14 weeks) were determined in an effort to ascertain the best time to harvest the plant for maximum medicinal quality with respect to its glucose-lowering effects. METHODS: The aqueous ethanolic leaf extracts of C. caudatus were characterized by NMR and LC-MS/MS. The total phenolic content and α-glucosidase inhibitory activity were evaluated by the Folin-Ciocalteu method and α-glucosidase inhibitory assay, respectively. The statistical significance of the results was evaluated using one-way ANOVA with Duncan's post hoc test, and correlation among the different activities was performed by Pearson's correlation test. NMR spectroscopy along with multivariate data analysis was used to identify the metabolites correlated with total phenolic content and α-glucosidase inhibitory activity of the C. caudatus leaf extracts. RESULTS: It was found that the α-glucosidase inhibitory activity and total phenolic content of the optimized ethanol:water (80:20) leaf extract of the plant increased significantly as the plant matured, reaching a maximum at the 10th week. The IC value for α-glucosidase inhibitory activity (39.18 μg mL) at the 10th week showed greater potency than the positive standard, quercetin (110.50 μg mL). Through an H NMR-based metabolomics approach, the 10-week-old samples were shown to be correlated with a high total phenolic content and α-glucosidase inhibitory activity. From the partial least squares biplot, rutin and flavonoid glycosides, consisting of quercetin 3-O-arabinofuranoside, quercetin 3-O-rhamnoside, quercetin 3-O-glucoside, and quercetin 3-O-xyloside, were identified as the major bioactive metabolites. The metabolites were identified by NMR spectroscopy (J-resolve, HSQC and HMBC experiments) and further supported by dereplication via LC-MS/MS. CONCLUSION: For high phytomedicinal quality, the 10th week is recommended as the best time to harvest C. caudatus leaves with respect to its glucose lowering potential.

Intramuscular autologous blood therapy - a systematic review of controlled trials.

Oomen-Welke K, Huber R

BMC Complement Altern Med · 2019 Sep · PMID 31488127 · Full text

BACKGROUND: Autologous whole blood (AWB) is used in complementary medicine for the treatment of infections and skin disorders. So far, the efficacy of AWB is discussed controversially. METHODS: To estimate the efficacy o... BACKGROUND: Autologous whole blood (AWB) is used in complementary medicine for the treatment of infections and skin disorders. So far, the efficacy of AWB is discussed controversially. METHODS: To estimate the efficacy of AWB therapy and to gather evidence in regard to effector mechanisms, we effected a systematic review of articles accessible through Pubmed and Cambase. Further trials were identified through references and by contacting study authors. Prospective controlled trials concerning intramuscular AWB therapy were included with the exception of trials using oxygenated, UV radiated or heated blood. Information was extracted on the indication, design, additions to AWB and outcome. Full texts were screened for information about the effector mechanisms. RESULTS: Eight trials suited our criteria. In three controlled trials about atopic dermatitis and urticaria, AWB therapy showed beneficial effects. In five randomized controlled trials (RCTs), two of which concerned respiratory tract infections, two urticaria and one ankylosing spondylitis, no efficacy could be found. A quantitative assessment was not possible due to the heterogeneity of the included studies. We only found four controlled trials with sample sizes bigger than 37 individuals per group. Only one study investigated the effector mechanisms of AWB. CONCLUSIONS: There is some evidence for efficacy of AWB therapy in urticaria patients and patients with atopic eczema. Firm conclusions can, however, not be drawn. We see a great need for further RCTs with adequate sample sizes and for investigation of the effector mechanisms of AWB therapy.

Microbial population dynamics under microdoses of the essential oil arborvitae.

McGregor RC, Parker KA, Hornby JM … +1 more , Latta LC

BMC Complement Altern Med · 2019 Sep · PMID 31488126 · Full text

BACKGROUND: With the current concern caused by drug resistant microorganisms, alternatives to traditional antimicrobials are increasingly necessary. Historical holistic treatments involving natural approaches are now of... BACKGROUND: With the current concern caused by drug resistant microorganisms, alternatives to traditional antimicrobials are increasingly necessary. Historical holistic treatments involving natural approaches are now of interest as a potential alternative. Many essential oils have antimicrobial properties with the ability to modify bacterial and fungal population dynamics in low concentrations. METHODS: In this study, bacterial and fungal growth in response to varying concentrations of arborvitae oil was assessed using spectrophotometric methods to obtain estimates of population growth parameters including carrying capacity (K) and intrinsic rate of growth (r). Estimates of these parameters were compared among doses within strains using general linear modeling. RESULTS: Results suggest the active component of the essential oil arborvitae is likely of hydrophilic nature and demonstrates the ability to influence both K and r during bacterial and fungal growth in a dose-dependent manner. Highly concentrated doses of arborvitae completely kill Escherichia coli and significantly inhibit Staphylococcus aureus, however these same doses have no effect on Pseudomonas aeruginosa. Accordingly, microdoses of arborvitae demonstrated the ability to inhibit population growth parameters in both prokaryotic and eukaryotic microorganisms. Specifically, K of E. coli, r of Candida auris, and both K and r of Candida albicans were significantly reduced in the presence of microdoses of arborvitae. CONCLUSIONS: Microdoses of essential oils have the ability to inhibit one or both population parameters in both prokaryotic and eukaryotic microorganisms. Some microorganisms appear to be more susceptible to this essential oil arborvitae than other microorganisms. The use of essential oils, such as arborvitae, as novel antimicrobials may prove useful when contending with the current epidemic of multidrug resistant pathogens.

Novel discovery of Averrhoa bilimbi ethanolic leaf extract in the stimulation of brown fat differentiation program in combating diet-induced obesity.

Lau WK, Noruddin NAA, Ariffin AH … +5 more , Mahmud MZ, Noor MHM, Amanah A, Hamzah MF, Zafarina Z

BMC Complement Altern Med · 2019 Sep · PMID 31488120 · Full text

BACKGROUND: Brown adipocytes are known to promote energy expenditure and limit weight gain to combat obesity. Averrhoa bilimbi, locally called belimbing buluh (DBB), is mainly used as an ethnomedicine in the treatment of... BACKGROUND: Brown adipocytes are known to promote energy expenditure and limit weight gain to combat obesity. Averrhoa bilimbi, locally called belimbing buluh (DBB), is mainly used as an ethnomedicine in the treatment of metabolic disorders including diabetes mellitus, hypertension and obesity. The present study aims to investigate the browning activity on white adipocytes by A. bilimbi leaf extract and to evaluate the potential mechanisms. METHODS: Ethanolic leaf extract of A. bilimbi was exposed to Myf5 lineage precursor cells to stimulate adipocyte differentiation. Protein expressions of brown adipocyte markers were determined through high content screening analysis and validated through western blotting. Mito Stress Test assay was conducted to evaluate the cellular oxygen consumption rate upon A. bilimbi treatment. RESULTS: A. bilimbi ethanolic leaf extract exhibited an adipogenesis effect similar to a PPARgamma agonist. It also demonstrated brown adipocyte differentiation in myoblastic Myf5-positive precursor cells. Expression of UCP1 and PRDM16 were induced. The basal metabolic rate and respiratory capacity of mitochondria were increased upon A. bilimbi treatment. CONCLUSIONS: The findings suggest that Averrhoa bilimbi ethanolic leaf extract induces adipocyte browning through PRDM16 activation and enhances mitochondria activity due to UCP1 up-regulation.

The protective effect and mechanism of catalpol on high glucose-induced podocyte injury.

Chen Y, Liu Q, Shan Z … +5 more , Zhao Y, Li M, Wang B, Zheng X, Feng W

BMC Complement Altern Med · 2019 Sep · PMID 31488111 · Full text

BACKGROUND: Catalpol, a natural iridoid glycoside in Rehmannia glutinosa, can alleviate proteinuria associated with diabetic nephropathy (DN), however, whether catalpol has a protective effect against podocyte injury in... BACKGROUND: Catalpol, a natural iridoid glycoside in Rehmannia glutinosa, can alleviate proteinuria associated with diabetic nephropathy (DN), however, whether catalpol has a protective effect against podocyte injury in DN remains unclear. METHODS: In this study, we used a high glucose (HG)-induced podocyte injury model to evaluate the protective effect and mechanism of catalpol against HG-induced podocyte injury. Cell viability was determined by the 3-(4,5-dimethylthiazolyl-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. The levels of lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdehyde (MDA) were measured by commercial assay kits. Cell apoptosis and reactive oxygen species (ROS) were determined by using flow cytometry. Tumour necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6) levels were determined by enzyme-linked immunosorbent assay (ELISA). The protein expression levels of B-cell lymphoma-2 (Bcl-2), Bcl2-associated x (Bax), cleaved caspase-3, nicotinamide adenine dinucleotide phosphate oxidase enzyme 4 (NOX4), toll-like receptor 4 (TLR4), myeloid differentiation primary response gene 88 (MyD88), p38 mitogen-activated protein kinase (p38 MAPK), phosphorylated p38 MAPK (p-p38 MAPK), nuclear factor kappa B inhibitor alpha (IκBα) and phosphorylated IκBα (p-IκBα) were measured by western blotting. In addition, Bcl-2, Bax, caspase-3 and nuclear factor kappa B (NF-κB) levels were determined by immunofluorescence staining. RESULTS: Catalpol significantly increased cell viability and decreased LDH release in HG-induced podocyte injury. Catalpol significantly decreased ROS generation, apoptosis, level of MDA, levels of inflammatory cytokine TNF-α, IL-1β, and IL-6 and increased SOD activity in HG-induced podocyte injury. Moreover, catalpol significantly decreased expression of cleaved caspase-3, Bax, NOX4, TLR4, MyD88, p-p38 MAPK, p-IκBα and NF-κB nuclear translocation, as well as increased Bcl-2 expression in HG-induced podocyte injury. CONCLUSION: Catalpol can protect against podocyte injury by ameliorating apoptosis and inflammation. These protective effects may be attributed to the inhibition of NOX4, which alleviates ROS generation and suppression of the TLR4/MyD88 and p38 MAPK signaling pathways to prevent NF-κB activation. Therefore, catalpol could be a promising drug for the prevention of DN.

Solid state fermentation process with Aspergillus kawachii enhances the cancer-suppressive potential of silkworm larva in hepatocellular carcinoma cells.

Cho HD, Min HJ, Won YS … +3 more , Ahn HY, Cho YS, Seo KI

BMC Complement Altern Med · 2019 Sep · PMID 31488109 · Full text

BACKGROUND: Mulberry silkworm larvae (Bombyx mori) are known as the oldest resource of food and traditional medicine. Although silkworm larvae have been reported to treat various chronic diseases, the effect of fermentat... BACKGROUND: Mulberry silkworm larvae (Bombyx mori) are known as the oldest resource of food and traditional medicine. Although silkworm larvae have been reported to treat various chronic diseases, the effect of fermentation by microorganisms improving the biological activities of silkworm larvae was not reported. In the present study, fermented silkworm larvae was developed via solid-state fermentation with Aspergillus kawachii and investigated its anti-cancer activity in human hepatocellular carcinoma cells. METHODS: We investigated the anti-cancer effects of unfermented (SEE) and fermented silkworm larva ethanol extract (FSEE) on HepG2 human hepatocellular carcinoma cells as well as compared changes in free amino acid, fatty acid, and mineral contents. Anti-cancer activities were evaluated by SRB staining, cell cycle analysis, Annexin V staining, Hoechst staining, DNA fragmentation analysis and western blot analysis. Fatty acid, free amino acid and mineral contents of SEE and FSEE were determined by gas chromatography, amino acid analyzer and flame atomic absorption spectrophotometer, respectively. RESULTS: Compared with SEE, treatment with FSEE resulted in apoptotic cell death in HepG2 cells characterized by G0/G1 phase cell cycle arrest, DNA fragmentation, and formation of apoptotic bodies. Furthermore, FSEE significantly up-regulated pro-apoptotic as well as down-regulated anti-apoptotic proteins in HepG2 cells. However, an equivalent concentration of SEE did not induce cell cycle arrest or apoptosis in HepG2 cells. Moreover, fermentation process by Aspergillus kawachii resulted in enhancement of fatty acid contents in silkworm larvae, whereas amino acid and mineral contents were decreased. CONCLUSION: Collectively, this study demonstrates that silkworm larvae solid state-fermented by Aspergillus kawachii strongly potentiates caspase-dependent and -independent apoptosis pathways in human hepatocellular carcinoma cells by regulating secondary metabolites.

Baihe Zhimu formula attenuates the efficacy of tamoxifen against breast cancer in mice through modulation of CYP450 enzymes.

Li H, Wu C, Liu Y … +2 more , Zhang S, Gao X

BMC Complement Altern Med · 2019 Sep · PMID 31484532 · Full text

BACKGROUND: Major depression is an important complication in patients with breast cancer, but is an underrecognized and undertreated condition in this population. The Baihe Zhimu Tang (BZ formula) is a traditional Chines... BACKGROUND: Major depression is an important complication in patients with breast cancer, but is an underrecognized and undertreated condition in this population. The Baihe Zhimu Tang (BZ formula) is a traditional Chinese formula consisting of Lilium brownii var. viridulum Baker (L. brownii) and Anemarrhena asphodeloides (A. asphodeloides) Bunge that is used for the treatment of depression. However, the interaction between tamoxifen and BZ formula is frequently overlooked by traditional and alternative medical doctors. In the present study, the influence of BZ formula on the effectiveness of tamoxifen in breast cancer in mice and the effects of tamoxifen on the antidepressant effect of BZ formula and its major components mangiferin and timosaponin BII in mice were investigated. METHODS: Identification of the major components of BZ formula was performed using fast HPLC-tandem mass spectrometry (HPLC-MS/MS). The main flavonoids and saponins in A. asphodeloides were determined by HPLC-UV and HPLC-ELSD, separately. The antidepressant efficacy of BZ formula was evaluated using a mouse tail-suspension test. The effects of BZ formula on the antineoplastic activity of tamoxifen were performed in a mouse xenograft model of human breast cancer MCF-7 cells. P450 activity was determined using microsomal incubations by HPLC-MS/MS. Measurement of serum concentrations of tamoxifen and its metabolites was used by HPLC-MS/MS. RESULTS: BZ formula attenuated the effectiveness of tamoxifen treatment of breast cancer and reduced the concentrations of endoxifen and 4-OH-tamoxifen in tumor-bearing mice. Of two of the major components of BZ formula, the antidepressant effect of mangiferin, but not timosaponin BII, was significantly inhibited by tamoxifen in mice. BZ formula and its component mangiferin also significantly inhibited CYP450 enzyme activity in rat liver microsomes. CONCLUSION: BZ formula attenuated the effectiveness of tamoxifen in treatment of breast cancer in mice by influencing CYP450 enzymes. The present study laid a foundation for the treatment of patients with breast cancer and depression by BZ formula or other Chinese herbal formulas containing A. asphodeloides.

The therapeutic effects of qigong in patients with chronic obstructive pulmonary disease in the stable stage: a meta-analysis.

Tong H, Liu Y, Zhu Y … +2 more , Zhang B, Hu J

BMC Complement Altern Med · 2019 Sep · PMID 31484521 · Full text

OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is one global disease. Lung function gradually declines. Medication does not fully reverse the airflow limitation. Qigong's role in COPD rehabilitation has been as... OBJECTIVES: Chronic obstructive pulmonary disease (COPD) is one global disease. Lung function gradually declines. Medication does not fully reverse the airflow limitation. Qigong's role in COPD rehabilitation has been assessed. We aimed to assess the effects of Qigong practised by COPD patients. METHODS: Eligible articles were obtained through a systematic search. The databased were search on October 8, 2017, and the date range of the searches in the electronic databases had no upper limit. The Cochrane risk-of-bias tool was used to evaluate the quality of the eligible studies. Mean differences with 95% confidence intervals were utilized to analyse the results. RESULTS: Ten included studies contained 993 participants. Statistical improvements occurred in the 6-min walk distance (6MWD) (MD, 30.57 m; 95% CI, 19.61-41.53 m; P < 0.00001); forced expiratory volume in 1 s (FEV1) (MD, 0.32 L; 95% CI, 0.09-0.56 L; P < 0.001); forced vital capacity rate of 1 s (FEV1/FVC) (MD, 2.66%; 95% CI, 1.32-2.26%; P = 0.0001); forced expiratory volume in 1 s/predicted (FEV1/pre) (MD, 6.04; CI, 2.58-9.5; P = 0.006); Monitored Functional Task Evaluation (MD, 0.88; 95% CI, 0.78-0.99; P < 0.00001); COPD Assessment Test for exercise (MD, - 5.54; 95% CI, - 9.49 to - 1.59; P = 0.006); Short Form-36 Health Quality Survey (SF-36)-General Health (MD, 5.22; 95% CI, 3.65-6.80; P < 0.00001); and Short Form-36 Health Quality Survey (SF-36)-Mental Health (MD, - 1.21; 95% CI, - 2.75 to 0.33; P = 0.12). CONCLUSIONS: In this meta-analysis of RCTs between ten included studies, we found that Qigong can improve COPD patients in lung function, exercise capacity and quality of life who were in the stable stage.

Inhibitory effect of purple rice husk extract on AFB-induced micronucleus formation in rat liver through modulation of xenobiotic metabolizing enzymes.

Chariyakornkul A, Punvittayagul C, Taya S … +1 more , Wongpoomchai R

BMC Complement Altern Med · 2019 Sep · PMID 31481128 · Full text

BACKGROUND: Rice husk, a waste material produced during milling, contains numerous phytochemicals that may be sources of cancer chemopreventive agents. Various biological activities of white and colored rice husk have be... BACKGROUND: Rice husk, a waste material produced during milling, contains numerous phytochemicals that may be sources of cancer chemopreventive agents. Various biological activities of white and colored rice husk have been reported. However, there are few comparative studies of the cancer chemopreventive effects of white and colored rice husk. METHODS: This study investigated the cancer chemopreventive activities of two different colors of rice husk using in vitro and in vivo models. A bacterial mutation assay using Salmonella typhimurium strains TA98 and TA100 was performed; enzyme induction activity in murine hepatoma cells was measured, and a liver micronucleus test was performed in male Wistar rats. RESULTS: The white rice husk (WRHE) and purple rice husk (PRHE) extracts were not mutagenic in Salmonella typhimurium TA98 or TA100 in the presence or absence of metabolic activation. However, the extracts exhibited antimutagenicity against aflatoxin B (AFB) and 2-amino-3,4 dimethylimidazo[4,5-f]quinolone (MeIQ) in a Salmonella mutation assay. The extracts also induced anticarcinogenic enzyme activity in a murine Hepa1c1c7 hepatoma cell line. Interestingly, PRHE but not WRHE exhibited antigenotoxicity in the rat liver micronucleus test. PRHE significantly decreased the number of micronucleated hepatocytes in AFB-initiated rats. PRHE contained higher amounts of phenolic compounds and vitamin E than WRHE in both tocopherols and tocotrienols as well as polyphenol such as cyanidin-3-glucoside, protocatechuic acid and vanillic acid. Furthermore, PRHE increased CYP1A1 and 1A2 activities while decreasing CYP3A2 activity in the livers of AFB-treated rats. PRHE also enhanced various detoxifying enzyme activities, including glutathione S-transferase, NAD(P)H quinone oxidoreductase and heme oxygenase. CONCLUSIONS: PRHE showed potent cancer chemopreventive activity in a rat liver micronucleus assay through modulation of phase I and II xenobiotic metabolizing enzymes involved in AFB metabolism. Vitamin E and phenolic compounds may be candidate antimutagens in purple rice husk.

Modulation of cancer signalling pathway(s) in two -stage mouse skin tumorigenesis by annonacin.

Md Roduan MR, Abd Hamid R, Mohtarrudin N

BMC Complement Altern Med · 2019 Sep · PMID 31481122 · Full text

BACKGROUND: Annonacin, an annonaceous acetogenin isolated from Annona muricata has been reported to be strongly cytotoxic against various cell lines, in vitro. Nevertheless, its effect against in vivo tumor promoting act... BACKGROUND: Annonacin, an annonaceous acetogenin isolated from Annona muricata has been reported to be strongly cytotoxic against various cell lines, in vitro. Nevertheless, its effect against in vivo tumor promoting activity has not been reported yet. Therefore, this study was aimed to investigate antitumor-promoting activity of annonacin via in vivo two-stage mouse skin tumorigenesis model and its molecular pathways involved. METHODS: Mice were initiated with single dose of 7,12-dimethylbenz[α]anthracene (DMBA) (390 nmol/100 μL) followed by, in subsequent week, repeated promotion (twice weekly; 22 weeks) with 12-O-tetradecanoylphorbol-13-acetate (TPA) (1.7 nmol/100 μL). Annonacin (85 nM) and curcumin (10 mg/kg; reference) were, respectively, applied topically to DMBA/TPA-induced mice 30 min before each TPA application for 22 weeks. Upon termination, histopathological examination of skin, liver and kidney as well as genes and proteins expression analysis were conducted to elucidate the potential mechanism of annonacin. RESULTS: With comparison to the carcinogen control, Annonacin significantly increased the tumor latency period and reduced the tumor incidence, tumor burden and tumor volume, respectively. In addition, it also suppressed tumorigenesis manifested by significant reduction of hyperkeratosis, dermal papillae and number of keratin pearls on skin tissues. Annonacin also appeared to be non-toxic to liver and kidney. Significant modulation of both AKT, ERK, mTOR, p38, PTEN and Src genes and proteins were also observed in annonacin-targeted signaling pathway(s) against tumorigenesis. CONCLUSIONS: Collectively, results of this study indicate that annonacin is a potential therapeutic compound targeting tumor promoting stage in skin tumorigenesis by modulating multiple gene and protein in cancer signaling pathways without apparent toxicity.

In vivo assessment of anticoagulant and antiplatelet effects of Syzygium cumini leaves extract in rabbits.

Rehman AA, Riaz A, Asghar MA … +3 more , Raza ML, Ahmed S, Khan K

BMC Complement Altern Med · 2019 Sep · PMID 31481052 · Full text

BACKGROUND: Syzygium cumini (L.) Skeels. is one of the very popular traditionally used medicinal plants with numerous pharmacological activities including antioxidant, hypoglycemic and anti-inflammatory. However, actions... BACKGROUND: Syzygium cumini (L.) Skeels. is one of the very popular traditionally used medicinal plants with numerous pharmacological activities including antioxidant, hypoglycemic and anti-inflammatory. However, actions of S. cumini on blood coagulation and other parameters of blood were poorly pharmacologically studied. Therefore, aim of this present investigation is to examine the effects of methanolic extract of S. cumini on blood coagulation and anticoagulation factors in healthy white albino rabbits at different doses. METHODS: Blood samples were drawn twice during this study and biochemical assays were performed to determine the effect on different parameters such as coagulation, anticoagulation, hematological, Protein C (PC) and thrombin antithrombin (TAT) complex and platelet aggregation. RESULTS: The results showed significant increase in RBCs, hemoglobin, hematocrit and platelets counts up to 1.4 × 10/cm, 2.2 g/dl, 6%, 248.2 × 10/cm respectively. While, thrombin and bleeding time were also prolonged in dose dependent manner which is highly significant (p ≤ 0.005) as compared to control. Similarly, highly significantly increased (p ≤ 0.005) in levels of protein C, thrombin antithrombin complex at dose of 500 mg/kg were observed. Whereas, levels of platelets aggregation and fibrinogen were decreased at high doses. CONCLUSION: The obtained findings of hematological and coagulation tests concludes possibly S. cumini possess anticoagulant and antiplatelet effects.

Comparative pharmacokinetics of oxyresveratrol alone and in combination with piperine as a bioenhancer in rats.

Junsaeng D, Anukunwithaya T, Songvut P … +3 more , Sritularak B, Likhitwitayawuid K, Khemawoot P

BMC Complement Altern Med · 2019 Sep · PMID 31477089 · Full text

BACKGROUND: Oxyresveratrol is a major bioactive component derived from the heartwood of Artocarpus lacucha. This compound exerts several biological activities, including neuroprotective effects in vitro and in vivo. Howe... BACKGROUND: Oxyresveratrol is a major bioactive component derived from the heartwood of Artocarpus lacucha. This compound exerts several biological activities, including neuroprotective effects in vitro and in vivo. However, there is limited pharmacokinetic information on this compound, especially its distribution in neuronal tissue and its route of excretion. The aim of this study was to investigate the pharmacokinetic profiles of oxyresveratrol alone and in combination with piperine as a bioenhancer in rats. METHODS: Male Wistar rats were administered with oxyresveratrol 10 mg/kg, oxyresveratrol 10 mg/kg plus piperine 1 mg/kg via intravenous or oxyresveratrol 100 mg/kg, oxyresveratrol 100 mg/kg plus piperine 10 mg/kg via oral gavage. Plasma, internal organs, urine, and feces were collected. Determination of the oxyresveratrol concentration in biological samples was performed by liquid chromatography tandem mass spectrometry. RESULTS: The combination with piperine had shown a significantly higher maximum concentration in plasma approximately 1500 μg/L within 1-2 h after oral dosing, and could increase oral bioavailability of oxyresveratrol approximately 2-fold. Oxyresveratrol could widely distributed most of the internal organs with a tissue to plasma ratio of 10-100 fold within 5 min after dosing. Urinary excretion of oxyresveratrol glucuronide was the major route of excretion after administration of oxyresveratrol alone and in combination with piperine. CONCLUSION: The addition of piperine could enhance some of the pharmacokinetic properties of oxyresveratrol via both intravenous and oral administration. This pharmacokinetic information will be useful for appropriate strategies to develop oxyresveratrol as a phytopharmaceutical product.
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