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Fulltext Safety and efficacy of tocotrienol supplementation for bone health in postmenopausal women: protocol for a dose-response double-blinded placebo-controlled randomised trial

Shen CL, Mo H, Yang S, Wang S, Felton CK, Tomison MD, et al.

BMJ Open, 2016 12 23;6(12):e012572.
PMID: 28011809 DOI: 10.1136/bmjopen-2016-012572

INTRODUCTION: Osteoporosis is a major health concern in postmenopausal women, and oxidative stress contributes to the development of bone loss. Cellular studies and ovariectomised rat model mimicking bone loss in postmenopausal women show the bone-protective effect of tocotrienols (TTs) with antioxidant capability. We aim to access the safety and efficacy of TT consumption for bone health in postmenopausal women.
METHODS AND ANALYSIS: In this 12-week randomised double-blinded placebo-controlled trial for the effects of dietary TT supplementation in postmenopausal women, postmenopausal women aged 45 years and older with at least 1 year after menopause and bone mineral density T-score at the spine and/or hip 2.5 or more below the reference values will be randomly assigned to 3 daily supplements: (1) placebo group receiving 860 mg olive oil, (2) low TT group receiving 430 mg of 70% pure TTs (containing 300 mg TT) and (3) high TT group receiving 860 mg of 70% pure TTs (600 mg TT). The primary outcome measure will be urinary N-terminal telopeptide. The secondary outcome measures will be serum bone-specific alkaline phosphatase, receptor activator of nuclear factor-κB ligand, osteoprotegerin, urinary 8-hydroxy-2'-deoxyguanosine and quality of life. At 0, 6 and 12 weeks, the following will be assessed: (1) primary and secondary outcome measures; (2) serum TT and tocopherol concentrations; (3) physical activity and food frequency questionnaires. Liver function will be monitored every 6 weeks for safety. 'Intent-to-treat' principle will be employed for data analysis. A model of repeated measurements with random effect error terms will be applied. Analysis of covariance, χ2 analysis and regression will be used for comparisons.
ETHICS AND DISSEMINATION: This study was approved by the Bioethics Committee of the Texas Tech University Health Sciences Center. The findings of this trial will be submitted to a peer-reviewed journal in the areas of bone or nutrition and international conferences.
TRIAL REGISTRATION NUMBER: NCT02058420; results.

Matched MeSH terms: Liver/drug effects
TROPHOBLASTIC TUMORS; GEOGRAPHICAL VARIATIONS IN INCIDENCE AND POSSIBLE AETIOLOGICAL FACTORS

LLEWELLYN-JONES D

J Obstet Gynaecol Br Commonw, 1965 Apr;72:242-8.
PMID: 14273103
Matched MeSH terms: Liver Function Tests*
Alpha-Fetoprotein levels in normal males from seven ethnic groups with different hepatocellular carcinoma risks

Sizaret P, Tuyns A, Martel N, Jouvenceaux A, Levin A, Ong YW, et al.

Ann N Y Acad Sci, 1975 Aug 22;259:136-55.
PMID: 54017

Alpha-Fetoprotein (AFP) levels of 1,335 males (15 years and older) of seven ethnic groups (Chinese, Indians, and Malays from Singapore, Caucasians from Lyon, and Blacks from Nairobi, forest, and the savanna region of the Ivory Coast) were determined by radioimmunoassay. A few elevated levels (up to 30 nanounits/ml) were detected in some normal individuals, especially in the older age-groups. In addition, there was a systematic age-dependency of AFP levels particularly evident in the groups from Singapore-Lyon, in which there was a 50% AFP increase between the ages of 20 and 40. Comparison between Africans on the one hand and people from Singapore-Lyon on the other hand revealed highly significant differences (p less than 0.001), especially in the younger groups, whereas Chinese, Malays, and Indians from Singapore had very similar AFP pattern; this suggests an important role for environmental factors in the regulation of AFP levels. The age dependency of the presumed effect of environmental factors is in keeping with experimental data showing that young animals respond more vigorously to AFP-stimulating factors. Although the incidence of hepatocellular carcinoma (HCC) differs in the three Singapore groups (the highest in Chinese and the lowest in Indians), no relationship was observed in this study between mean AFP level and HCC incidence in Singapore.

Matched MeSH terms: Liver Neoplasms/blood*
Sunitinib-paracetamol sex-divergent pharmacokinetics and tissue distribution drug-drug interaction in mice

Liew MH, Ng S, Chew CC, Koo TW, Chee YL, Chee EL, et al.

Invest New Drugs, 2017 04;35(2):145-157.
PMID: 28070719 DOI: 10.1007/s10637-016-0415-y

The sex-divergent pharmacokinetics and interaction of tyrosine kinase inhibitor sunitinib with paracetamol was evaluated in male and female mice. Mice (control groups) were administered 60 mg/kg PO sunitinib alone or with 200 mg/kg PO paracetamol (study groups). Sunitinib concentration in plasma, brain, kidney and liver were determined and non-compartmental pharmacokinetic analysis performed. Female control mice showed 36% higher plasma sunitinib AUC0→∞, 31% and 27% lower liver and kidney AUC0→∞ and 2.2-fold higher AUC0→∞ in brain (all p liver- and kidney-to-plasma AUC0→∞ ratios (p liver (15%, 9%), kidney (15%, 20%) and brain (47%, 50%) AUC0→∞ (p

Matched MeSH terms: Liver/metabolism
Diclofenac sex-divergent drug-drug interaction with Sunitinib: pharmacokinetics and tissue distribution in male and female mice

Chew CC, Ng S, Chee YL, Koo TW, Liew MH, Chee EL, et al.

Invest New Drugs, 2017 08;35(4):399-411.
PMID: 28285369 DOI: 10.1007/s10637-017-0447-y

Coadministration of diclofenac and sunitinib, tyrosine kinase inhibitor, led to sex-divergent pharmacokinetic drug-drug interaction outcomes. Male and female mice were administered 60 mg/kg PO sunitinib alone (control groups) or with 30 mg/kg PO diclofenac. Sunitinib concentration in plasma, brain, kidney and liver were determined by HPLC and non-compartmental pharmacokinetic parameters calculated. In male mice, diclofenac decreased AUC0→∞ 38% in plasma (p liver (p liver uptake efficiency in male (27%, p

Matched MeSH terms: Liver/metabolism
Sengstaken-Blakemore tube malposition with esophageal rupture

Chuah YY, Lee YY, Chen WC, Kao SS

Acta Gastroenterol Belg, 2018 10 24;81(3):447-448.
PMID: 30350541
Matched MeSH terms: Liver Cirrhosis/complications
Withaferin A Protects Against High-Fat Diet-Induced Obesity Via Attenuation of Oxidative Stress, Inflammation, and Insulin Resistance

Abu Bakar MH, Azmi MN, Shariff KA, Tan JS

Appl Biochem Biotechnol, 2019 May;188(1):241-259.
PMID: 30417321 DOI: 10.1007/s12010-018-2920-2

Withaferin A (WA), a bioactive constituent derived from Withania somnifera plant, has been shown to exhibit many qualifying properties in attenuating several metabolic diseases. The current investigation sought to elucidate the protective mechanisms of WA (1.25 mg/kg/day) on pre-existing obese mice mediated by high-fat diet (HFD) for 12 weeks. Following dietary administration of WA, significant metabolic improvements in hepatic insulin sensitivity, adipocytokines with enhanced glucose tolerance were observed. The hepatic oxidative functions of obese mice treated with WA were improved via augmented antioxidant enzyme activities. The levels of serum pro-inflammatory cytokines and hepatic mRNA expressions of toll-like receptor (TLR4), nuclear factor κB (NF-κB), tumor necrosis factor-α (TNF-α), chemokine (C-C motif) ligand-receptor, and cyclooxygenase 2 (COX2) in HFD-induced obese mice were reduced. Mechanistically, WA increased hepatic mRNA expression of peroxisome proliferator-activated receptors (PPARs), cluster of differentiation 36 (CD36), fatty acid synthase (FAS), carnitine palmitoyltransferase 1 (CPT1), glucokinase (GCK), phosphofructokinase (PFK), and phosphoenolpyruvate carboxykinase (PCK1) that were associated with enhanced lipid and glucose metabolism. Taken together, these results indicate that WA exhibits protective effects against HFD-induced obesity through attenuation of hepatic inflammation, oxidative stress, and insulin resistance in mice.

Matched MeSH terms: Fatty Liver/prevention & control
Fulltext Lipopolysaccharide, immune activation, and liver abnormalities in HIV/hepatitis B virus (HBV)-coinfected individuals receiving HBV-active combination antiretroviral therapy

Crane M, Avihingsanon A, Rajasuriar R, Velayudham P, Iser D, Solomon A, et al.

J Infect Dis, 2014 Sep 1;210(5):745-51.
PMID: 24585898 DOI: 10.1093/infdis/jiu119

We investigated the relationship between microbial translocation, immune activation, and liver disease in human immunodeficiency virus (HIV)/hepatitis B virus (HBV) coinfection. Lipopolysaccharide (LPS), soluble CD14, CXCL10, and CCL-2 levels were elevated in patients with HIV/HBV coinfection. Levels of LPS, soluble CD14, and CCL-2 declined following receipt of HBV-active combination antiretroviral therapy (cART), but the CXCL10 level remained elevated. No markers were associated with liver disease severity on liver biopsy (n = 96), but CXCL10, interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor α, and interferon γ (IFN-γ) were all associated with elevated liver enzyme levels during receipt of HBV-active cART. Stimulation of hepatocyte cell lines in vitro with IFN-γ and LPS induced a profound synergistic increase in the production of CXCL10. LPS may contribute to liver disease via stimulating persistent production of CXCL10.

Matched MeSH terms: Liver/pathology*
The silvered leaf-monkey of Malaysia, Presbytis cristatus: disease model for human scrub typhus

Walker JS, Cadigan FC, Vosdingh RA, Chye CT

J Infect Dis, 1973 Aug;128(2):223-6.
PMID: 4198721
Matched MeSH terms: Liver/microbiology
Fulltext Honeycomb and necklace signs in liver abscesses secondary to melioidosis

Ong SCL, Alemam MMM, Zakaria NA, Abdul Halim NA

BMJ Case Rep, 2017 Oct 19;2017.
PMID: 29054959 DOI: 10.1136/bcr-2017-222342

Melioidosis is endemic in Southeast Asia and tropical Australia with varying clinical features from benign skin lesions to fatal septicaemia. Imaging plays an important role in evaluation of the melioid liver abscesses. A 45-year-old man with underlying diabetes presented with fever and lethargy for 2 weeks and abdominal pain for 2 days. His liver was enlarged on examination. Blood investigations revealed mild leucocytosis and raised liver enzymes. Ultrasound showed multiple multiloculated hypoechoic lesions throughout the liver and spleen. CT of abdomen confirmed that some liver lesions were made up of asymmetric locules of varying sizes (honeycomb sign), while others had hypodense centre with small symmetric peripheral locules in radial fashion (necklace sign). Blood culture was positive for Burkholderia pseudomallei He was subsequently treated with ceftazidime for a month followed by oral trimethoprim-sulfamethoxazole for 3 months. Follow-up CT of abdomen a month after diagnosis and treatment showed resolving hepatic and splenic lesions.

Matched MeSH terms: Liver Abscess/etiology
Perilipin 5 Deletion Unmasks an Endoplasmic Reticulum Stress-Fibroblast Growth Factor 21 Axis in Skeletal Muscle

Montgomery MK, Mokhtar R, Bayliss J, Parkington HC, Suturin VM, Bruce CR, et al.

Diabetes, 2018 04;67(4):594-606.
PMID: 29378767 DOI: 10.2337/db17-0923

Lipid droplets (LDs) are critical for the regulation of lipid metabolism, and dysregulated lipid metabolism contributes to the pathogenesis of several diseases, including type 2 diabetes. We generated mice with muscle-specific deletion of the LD-associated protein perilipin 5 (PLIN5, Plin5MKO ) and investigated PLIN5's role in regulating skeletal muscle lipid metabolism, intracellular signaling, and whole-body metabolic homeostasis. High-fat feeding induced changes in muscle lipid metabolism of Plin5MKO mice, which included increased fatty acid oxidation and oxidative stress but, surprisingly, a reduction in inflammation and endoplasmic reticulum (ER) stress. These muscle-specific effects were accompanied by whole-body glucose intolerance, adipose tissue insulin resistance, and reduced circulating insulin and C-peptide levels in Plin5MKO mice. This coincided with reduced secretion of fibroblast growth factor 21 (FGF21) from skeletal muscle and liver, resulting in reduced circulating FGF21. Intriguingly, muscle-secreted factors from Plin5MKO , but not wild-type mice, reduced hepatocyte FGF21 secretion. Exogenous correction of FGF21 levels restored glycemic control and insulin secretion in Plin5MKO mice. These results show that changes in lipid metabolism resulting from PLIN5 deletion reduce ER stress in muscle, decrease FGF21 production by muscle and liver, and impair glycemic control. Further, these studies highlight the importance for muscle-liver cross talk in metabolic regulation.

Matched MeSH terms: Liver/metabolism*
Hepatitis markers in Malaysians with hepatocellular carcinoma

Lopez JB, Thambyrajah V, Balasegaram M, Satgunasingam N

Br J Biomed Sci, 1994 Jun;51(2):177-80.
PMID: 7519505

Sera from 80 Malaysians with confirmed hepatocellular carcinoma were tested for five markers of the hepatitis B virus, anti-HCV and anti-HDV by enzyme immunoassay, and alpha fetoprotein (AFP) was measured by radioimmunoassay. Of the patients, 98.8% had evidence of HBV infection and 75% were positive for HBsAg--which latter correlated with AFP raised above cut-off values of 500 ng/ml (P = 0.0001) and 200 ng/ml (P = 0.005). Males correlated significantly with the presence of HBsAg (P = 0.002). Thirty-one per cent of HBsAg positive patients were also positive for HBeAg and 74% for anti-HBe. Twenty per cent of the cases were concurrently positive for both HBsAg and anti-HBs. Six of 70 (8.6%) patients were positive for anti-HCV, of whom four were also positive for HBsAg. None of 67 patients tested for anti-HDV were positive. The results strongly indicate an important aetiological role for hepatitis B virus in causation of hepatocellular carcinoma among Malaysians.

Matched MeSH terms: Liver Neoplasms/microbiology*
Fulltext Sarcoidosis: a review of cases seen at the University Hospital, Kuala Lumpur

Liam CK, Menon A

Singapore Med J, 1993 Apr;34(2):153-6.
PMID: 8266159

Fourteen cases of sarcoidosis consisting of 7 male and 7 female patients with a mean age of 42.4 years were seen at the University Hospital from 1972 to 1990. There were 10 Indians, 2 Malays, and 2 Chinese. Twelve patients had thoracic involvement. The other common disease manifestations included weight loss, arthralgia, hepatomegaly, erythema nodosum, peripheral lymphadenopathy, and hypercalcaemia. At initial presentation, the disease was in radiographic stage I, II, and III in 8, 3 and one patient respectively. The Kveim test was positive in 7 out of 9 patients. Eight patients required steroid therapy.

Matched MeSH terms: Liver Diseases/physiopathology
Fuzzy logic and adaptive neuro-fuzzy inference system for characterization of contaminant exposure through selected biomarkers in African catfish

Karami A, Keiter S, Hollert H, Courtenay SC

Environ Sci Pollut Res Int, 2013 Mar;20(3):1586-95.
PMID: 22752811 DOI: 10.1007/s11356-012-1027-5

This study represents a first attempt at applying a fuzzy inference system (FIS) and an adaptive neuro-fuzzy inference system (ANFIS) to the field of aquatic biomonitoring for classification of the dosage and time of benzo[a]pyrene (BaP) injection through selected biomarkers in African catfish (Clarias gariepinus). Fish were injected either intramuscularly (i.m.) or intraperitoneally (i.p.) with BaP. Hepatic glutathione S-transferase (GST) activities, relative visceral fat weights (LSI), and four biliary fluorescent aromatic compounds (FACs) concentrations were used as the inputs in the modeling study. Contradictory rules in FIS and ANFIS models appeared after conversion of bioassay results into human language (rule-based system). A "data trimming" approach was proposed to eliminate the conflicts prior to fuzzification. However, the model produced was relevant only to relatively low exposures to BaP, especially through the i.m. route of exposure. Furthermore, sensitivity analysis was unable to raise the classification rate to an acceptable level. In conclusion, FIS and ANFIS models have limited applications in the field of fish biomarker studies.

Matched MeSH terms: Liver/enzymology
The combined effect of hypoxia and nutritional status on metabolic and ionoregulatory responses of common carp (Cyprinus carpio)

Moyson S, Liew HJ, Diricx M, Sinha AK, Blust R, De Boeck G

Comp Biochem Physiol A Mol Integr Physiol, 2015 Jan;179:133-43.
PMID: 25263807 DOI: 10.1016/j.cbpa.2014.09.017

In the present study, the combined effects of hypoxia and nutritional status were examined in common carp (Cyprinus carpio), a relatively hypoxia tolerant cyprinid. Fish were either fed or fasted and were exposed to hypoxia (1.5-1.8mg O2L(-1)) at or slightly above their critical oxygen concentration during 1, 3 or 7days followed by a 7day recovery period. Ventilation initially increased during hypoxia, but fasted fish had lower ventilation frequencies than fed fish. In fed fish, ventilation returned to control levels during hypoxia, while in fasted fish recovery only occurred after reoxygenation. Due to this, C. carpio managed, at least in part, to maintain aerobic metabolism during hypoxia: muscle and plasma lactate levels remained relatively stable although they tended to be higher in fed fish (despite higher ventilation rates). However, during recovery, compensatory responses differed greatly between both feeding regimes: plasma lactate in fed fish increased with a simultaneous breakdown of liver glycogen indicating increased energy use, while fasted fish seemed to economize energy and recycle decreasing plasma lactate levels into increasing liver glycogen levels. Protein was used under both feeding regimes during hypoxia and subsequent recovery: protein levels reduced mainly in liver for fed fish and in muscle for fasted fish. Overall, nutritional status had a greater impact on energy reserves than the lack of oxygen with a lower hepatosomatic index and lower glycogen stores in fasted fish. Fasted fish transiently increased Na(+)/K(+)-ATPase activity under hypoxia, but in general ionoregulatory balance proved to be only slightly disturbed, showing that sufficient energy was left for ion regulation.

Matched MeSH terms: Liver/metabolism
Fulltext Metagenomic and phytochemical analyses of kefir water and its subchronic toxicity study in BALB/c mice

Kumar MR, Yeap SK, Mohamad NE, Abdullah JO, Masarudin MJ, Khalid M, et al.

BMC Complement Med Ther, 2021 Jul 01;21(1):183.
PMID: 34210310 DOI: 10.1186/s12906-021-03358-3

BACKGROUND: In recent years, researchers are interested in the discovery of active compounds from traditional remedies and natural sources, as they reveal higher therapeutic efficacies and improved toxicological profiles. Among the various traditional treatments that have been widely studied and explored for their potential therapeutic benefits, kefir, a fermented beverage, demonstrates a broad spectrum of pharmacological properties, including antioxidant, anti-inflammation, and healing activities. These health-promoting properties of kefir vary among the kefir cultures found at the different part of the world as different media and culture conditions are used for kefir maintenance and fermentation.
METHODS: This study investigated the microbial composition and readily found bioactive compounds in water kefir fermented in Malaysia using 16S rRNA microbiome and UHPLC sequencing approaches. The toxicity effects of the kefir water administration in BALB/c mice were analysed based on the mice survival, body weight index, biochemistry profile, and histopathological changes. The antioxidant activities were evaluated using SOD, FRAP, and NO assays.
RESULTS: The 16S rRNA amplicon sequencing revealed the most abundant species found in the water kefir was Lactobacillus hilgardii followed by Lactobacillus harbinensis, Acetobacter lovaniensis, Lactobacillus satsumensis, Acetobacter tropicalis, Lactobacillus zeae, and Oenococcus oeni. The UHPLC screening showed flavonoid and phenolic acid derivatives as the most important bioactive compounds present in kefir water which has been responsible for its antioxidant activities. Subchronic toxicity study showed no toxicological signs, behavioural changes, or adverse effects by administrating 10 mL/kg/day and 2.5 mL/kg/day kefir water to the mice. Antioxidants assays demonstrated enhanced SOD and FRAP activities and reduced NO level, especially in the brain and kidney samples.
CONCLUSIONS: This study will help to intensify the knowledge on the water kefir microbial composition, available phytochemicals and its toxicological and antioxidant effects on BALB/c mice since there are very limited studies on the water kefir grain fermented in Malaysia.

Matched MeSH terms: Liver/metabolism
Fulltext Rational design and synthesis of novel diphenyl ether derivatives as antitubercular agents

Kar SS, Bhat G V, Rao PP, Shenoy VP, Bairy I, Shenoy GG

Drug Des Devel Ther, 2016;10:2299-310.
PMID: 27486307 DOI: 10.2147/DDDT.S104037

A series of triclosan mimic diphenyl ether derivatives have been synthesized and evaluated for their in vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The binding mode of the compounds at the active site of enoyl-acyl carrier protein reductase of M. tuberculosis has been explored. Among them, compound 10b was found to possess antitubercular activity (minimum inhibitory concentration =12.5 µg/mL) comparable to triclosan. All the synthesized compounds exhibited low levels of cytotoxicity against Vero and HepG2 cell lines, and three compounds 10a, 10b, and 10c had a selectivity index more than 10. Compound 10b was also evaluated for log P, pKa, human liver microsomal stability, and % protein binding, in order to probe its druglikeness. Based on the antitubercular activity and druglikeness profile, it may be concluded that compound 10b could be a lead for future development of antitubercular drugs.

Matched MeSH terms: Microsomes, Liver/drug effects
Fulltext IN VIVO CARBON TETRACHLORIDE-INDUCED HEPATOPROTECTIVE AND IN VITRO CYTOTOXIC ACTIVITIES OF GARCINIA HOMBRONIANA (SEASHORE MANGOSTEEN)

Jamila N, Khan N, Khan AA, Khan I, Khan SN, Zakaria ZA, et al.

Afr J Tradit Complement Altern Med, 2017;14(2):374-382.
PMID: 28573253 DOI: 10.21010/ajtcam.v14i2.38

BACKGROUND: Garcinia hombroniana, known as "manggis hutan" (jungle mangosteen) in Malaysia, is distributed in tropical Asia, Borneo, Thailand, Andaman, Nicobar Islands, Vietnam and India. In Malaysia, its ripened crimson sour fruit rind is used as a seasoning agent in curries and culinary dishes. Its roots and leaves decoction is used against skin infections and after child birth. This study aimed to evaluate in vivo hepatoprotective and in vitro cytotoxic activities of 20% methanolic ethyl acetate (MEA) G. hombroniana bark extract.
MATERIALS AND METHODS: In hepatoprotective activity, liver damage was induced by treating rats with 1.0 mL carbon tetrachloride (CCl4)/kg and MEA extract was administered at a dose of 50, 250 and 500 mg/kg 24 h before intoxication with CCl4. Cytotoxicity study was performed on MCF-7 (human breast cancer), DBTRG (human glioblastoma), PC-3 (human prostate cancer) and U2OS (human osteosarcoma) cell lines. 1H, 13C-NMR (nuclear magnetic resonance), and IR (infrared) spectral analyses were also conducted for MEA extract.
RESULTS: In hepatoprotective activity evaluation, MEA extract at a higher dose level of 500 mg/kg showed significant (p<0.05) potency. In cytotoxicity study, MEA extract was more toxic towards MCF-7 and DBTRG cell lines causing 78.7% and 64.3% cell death, respectively. MEA extract in 1H, 13C-NMR, and IR spectra exhibited bands, signals and J (coupling constant) values representing aromatic/phenolic constituents.
CONCLUSIONS: From the results, it could be concluded that MEA extract has potency to inhibit hepatotoxicity and MCF-7 and DBTRG cancer cell lines which might be due to the phenolic compounds depicted from NMR and IR spectra.

Matched MeSH terms: Drug-Induced Liver Injury/prevention & control*
Fulltext Natural Compounds from Hatikana Extract Potentiate Antidiabetic Actions as Displayed by In Vivo Assays and Verified by Network Pharmacological Tools

Rahman MA, Uddin MN, Babteen NA, Alnajeebi AM, Zakaria ZA, Aboelenin SM

Biomed Res Int, 2021;2021:6978450.
PMID: 34725640 DOI: 10.1155/2021/6978450

BACKGROUND: Hatikana is a traditional medicinal plant used to treat inflammation, urolithiasis, goiter, cancer, wounds and sores, gastrointestinal, tumor, tetanus, arthritis, hepatic damage, neurodegeneration, and other ailments. The goal of this study is to investigate the antidiabetic properties of Hatikana extract (HKEx) and to construct the effects of its natural constituents on the genes and biochemical indices that are connected with them.
METHODS: HKEx was evaluated using GC-MS and undertaken for a three-week intervention in fructose-fed STZ-induced Wistar albino rats at the doses of HKEx50, HKEx100, and HKEx200 mg/kg bw. Following intervention, blood serum was examined for biochemical markers, and liver tissue was investigated for the mRNA expression of catalase (CAT), glutathione peroxidase (GPx), and superoxide dismutase (SOD1) by RTPCR analysis. Most abundant compounds (oleanolic acid, 7α, 28-olean diol, and stigmasterol) from GC-MS were chosen for the network pharmacological assay to verify function-specific gene-compound interactions using STITCH, STRING, GSEA, and Cytoscape plugin cytoHubba.
RESULTS: In vivo results showed a significant (P < 0.05) decrease of blood sugar, aspartate aminotransferase (AST), alanine aminotransferase (ALT), creatinine kinase (CK-MB), and lactate dehydrogenase (LDH) and increase of liver glycogen, glucose load, and serum insulin. Out of three antioxidative genes, catalase (CAT) and superoxide dismutase (SOD1) were found to be few fold increased. Oleanolic acid and stigmasterol were noticed to strongly interact with 27 target proteins. Oleanolic acid interacted with the proteins AKR1B10, CASP3, CASP8, CYP1A2, CYP1A2, HMGB1, NAMPT, NFE2L2, NQO1, PPARA, PTGIR, TOP1, TOP2A, UGT2B10, and UGT2B11 and stigmasterol with ABCA1, ABCG5, ABCG8, CTSE, HMGCR, IL10, CXCL8, NR1H2, NR1H3, SLCO1B1, SREBF2, and TNF. Protein-protein interaction (PPI) analysis revealed the involvement of 25 target proteins out of twenty seven. Cytoscape plugin cytoHubba identified TNF, CXCL8, CASP3, PPARA, SREBF2, and IL10 as top hub genes. Pathway analysis identified 31 KEGG metabolic, signaling, and immunogenic pathways associated with diabetes. Notable degree of PPI enrichment showed that SOD1 and CAT are responsible for controlling signaling networks and enriched pathways.
CONCLUSION: The findings show that antioxidative genes have regulatory potential, allowing the HKEx to be employed as a possible antidiabetic source pending further validation.

Matched MeSH terms: Liver/pathology
Effect of permeation enhancers in the mucoadhesive buccal patches of salbutamol sulphate for unidirectional buccal drug delivery

Prasanth VV, Puratchikody A, Mathew ST, Ashok KB

Res Pharm Sci, 2014 Jul-Aug;9(4):259-68.
PMID: 25657797

The purpose of this work was to study the effect of various permeation enhancers on the permeation of salbutamol sulphate (SS) buccal patches through buccal mucosa in order to improve the bioavailability by avoiding the first pass metabolism in the liver and possibly in the gut wall and also achieve a better therapeutic effect. The influence of various permeation enhancers, such as dimethyl sulfoxide (DMSO), linoleic acid (LA), isopropyl myristate (IPM) and oleic acid (OA) on the buccal absorption of SS from buccal patches containing different polymeric combinations such as hydroxypropyl methyl cellulose (HPMC), carbopol, polyvinyl alcohol (PVA), polyvinyl pyrollidone (PVP), sodium carboxymethyl cellulose (NaCMC), acid and water soluble chitosan (CHAS and CHWS) and Eudragit-L100 (EU-L100) was investigated. OA was the most efficient permeation enhancer increasing the flux greater than 8-fold compared with patches without permeation enhancer in HPMC based buccal patches when PEG-400 was used as the plasticizer. LA also exhibited a better permeation enhancing effect of over 4-fold in PVA and HPMC based buccal patches. In PVA based patches, both OA and LA were almost equally effective in improving the SS permeation irrespective of the plasticizer used. DMSO was more effective as a permeation enhancer in HPMC based patches when PG was the plasticizer. IPM showed maximum permeation enhancement of greater than 2-fold when PG was the plasticizer in HPMC based buccal patches.

Matched MeSH terms: Liver

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