scholarly journals Enhanced Pharmacological Efficacy of Berberine Hydrochloride Loaded Lipid Based Pellets for the Treatment of Metabolic Diseases

2021 ◽  
Vol 14 (02) ◽  
pp. 993-1005
Author(s):  
Rakesh V. Mishra ◽  
Shashikant N. Dhole
Keyword(s):  
Oral Dose ◽  
Dose Level ◽  
Metabolic Diseases ◽  
Calorie Intake ◽  
High Dose ◽  
Therapeutic Effects ◽  
Reference Drug ◽  
Berberine Hydrochloride ◽  
Systemic Bioavailability ◽  
Male Wistar Rats

Numerous researchers in past have reported the diversified therapeutic effects of Berberine hydrochloride (BERH) for the management of metabolic diseases, however due to poor systemic bioavailability these effects are dose dependant and desired effects were reported at high dose levels. The objective of present investigation is to evaluate and establish the enhancement in pharmacological efficacy of the designed BERH formulation at low oral dose level for the treatment of metabolic diseases constituting metabolic syndrome (MS). In the present investigation, BERH formulation in the dose level of (25 and 50mg/kg/day) was evaluated in cafeteria diet (CD) induced MS model in male Wistar rats for 42 days and compared with available marketed preparation in similar dose level using orlistat as reference drug. Among the studied dose level of BERH formulation the 25 mg/kg/day dose was adequate to produce significant reduction in calorie intake (P < 0.01), body weight, BMI, (P<0.001), organ weight viz. (stomach; P<0.05, liver; P<0.001, heart; P<0.01) and serum biochemical parameters (P<0.001). A significant improvement in lipid peroxidation (P<0.001), catalase (CAT), reduced glutathione (GSH) and superoxide dismutase (SOD) contents (P<0.001) was observed. The histopathological examinations indicated amelioration of liver, heart and pancreas tissues. The current study indicated significant glucose-lowering, hypophagic, anti-obesity, anti-hyperlipidemic and cardio protective activity of the BERH formulation even in much low oral dose level compared to previously reported studies. The observed behavior is attributed due to the enhanced bioavailability of BERH formulation which could be effectively used for metabolic diseases treatment.

Adipose Tissue Remodeling by Prolonged Administration of High Dose of Vitamin D3 in Rats Treated to Prevent Sarcopenia

2017 ◽  
Vol 68 (9) ◽  
pp. 2139-2143 ◽  
Author(s):  
Alin Constantin Pinzariu ◽  
Sorin Aurelian Pasca ◽  
Allia Sindilar ◽  
Cristian Drochioi ◽  
Mihail Balan ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Vitamin D3 ◽  
Term Treatment ◽  
High Dose ◽  
Omental Adipose Tissue ◽  
Long Term Treatment ◽  
Male Wistar Rats ◽  
Adipose Tissue Remodeling ◽  
Visceral Adipose

To examine the effect of high dose vitamin D3 treatment on visceral adipose tissue, we used vitamin D deficient male Wistar rats (18 months old) as a model of sarcopenia. The aging process is not only responsive for the losing muscle mass but also for redistribution of lipid resulting in altered fatty acid storage and dysdifferentiation of mesenchymal precursors. The effect of aging and vitamin D treatment (weekly oral gavage with 0.125 mg vitamin D3 (5000 IU)/100g body weight) on the omental adipose tissue were histological examinated. At the end of the experiment (9 monhs), adaptive changes to the reduction of adipogenesis and increased apoptosis in response to long-term treatment with vitamin D consisted of smaller size of adipocyte and moderate macrophage infiltrate.

HAEMATO-BIOCHEMICAL AND IMMUNOLOGICAL CHANGES IN EXPERIMENTALLY INDUCED ACETAMIPRID TOXICITY IN SWISS ALBINO MICE

2016 ◽  
Vol 12 (1) ◽  
Author(s):  
D.T. Fefar ◽  
Ankita N. Brahmbhatt ◽  
B.P. Joshi ◽  
D.J. Ghodasara
Keyword(s):  
Dose Level ◽  
Significant Rise ◽  
High Dose ◽  
Cell Mediated Immunity ◽  
Swiss Albino Mice ◽  
Mean Values ◽  
Group Iii ◽  
Treatment Groups ◽  
Immunological Effects ◽  
Albino Mice

A study was conducted on 5 weeks old 64 (32 male and 32 female) Swiss albino mice to assess the haemato-biochemical and immunological effects of acetamiprid. All the male and female mice were randomly divided into eight different groups. The groups I (male) and II (female) served as controls whereas remaining groups served as treatment groups and were administered acetamiprid at the daily dose rate of 20, 10, 5 mg/kg body weight in males(Group III, V, VII) and females (Group IV, VI,VIII),respectively for 28 days. After 28 days treatment, blood samples were collected for hematological, biochemical as well as immunological analysis. There was significant decrease in haematological parameters like Hb, TEC, TLC, neutrophils and lymphocytes count in high dose groups and revealed potential adversity of acetamiprid at rates of 20 mg/kg/day on haematopoetic system of mice. A dose dependent significant rise in mean values of AST and ALT was observed in treatment groups, whereas there was significant decrease in total protein and albumin and increase in BUN in high and mid dose treated groups, irrespective of sex of mice. Dinitroflurobenzene (DNFB) test conducted to assess the cell mediated immunity revealed the toxic effect of acetamiprid on cell mediated immunity of mice at dose level of 10 mg/kg/day. The mice of high dose group revealed a significant decrease in HA titer and indicated the immunotoxic potential of acetamiprid at dose level of 20 mg/kg/day.

scholarly journals Icariin protects against cage layer osteoporosis by intervening in steroid biosynthesis and glycerophospholipid metabolism

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Zhengwang Yu ◽  
Jie Huang ◽  
Zhongxin Zhou
Keyword(s):  
Metabolic Diseases ◽  
Chinese Herb ◽  
Therapeutic Effects ◽  
Mineral Density ◽  
Steroid Biosynthesis ◽  
Metabolic Pathway Analysis ◽  
Effective Prevention ◽  
Calcium Diet ◽  
Low Calcium Diet ◽  
Low Calcium

AbstractCage layer osteoporosis (CLO) is a common bone metabolism disease in the breeding industry of China. However, effective prevention for CLO has not been developed. Icariin (ICA), the main bioactive component of the Chinese herb Epimedium, has been shown to have good therapeutic effects on bone-related diseases. In this study, the effects of ICA were further evaluated in a low-calcium diet-induced CLO, and a serum metabolomics assay was performed to understand the underlying mechanisms. A total of 144 31-wk-old Lohmann pink-shell laying hens were randomly allocated to 4 groups with 6 replicates of 6 hens per replicate. The 4 dietary treatment groups consisted of a basal diet (3.5% calcium), a low-calcium diet (2.0% calcium), and a low-calcium diet supplemented with 0.5 or 2.0 g/kg ICA. The results showed that ICA exerted good osteoprotective effects on low-calcium diet-induced CLO. ICA significantly increased femur bone mineral density, improved bone microstructure, decreased bone metabolic level, and upregulated mRNA expression of bone formation genes in femoral bone tissue. Serum untargeted metabolomics analysis showed that 8 metabolite levels were significantly changed after ICA treatment, including increased contents of 7-dehydrocholesterol, 7-oxocholesterol, desmosterol, PC (18:1(9Z)/18:1(9Z)), PS (18:0/18:1(9Z)), N,N-dimethylaniline and 2-hydroxy-butanoic acid and decreased N2,N2-dimethylguanosine. Metabolic pathway analysis based on the above 8 metabolites indicated that ICA mainly perturbed steroid biosynthesis and glycerophospholipid metabolism. These findings suggest that ICA can effectively prevent bone loss in low-calcium diet-induced CLO by mediating steroid biosynthesis and glycerophospholipid metabolism and provide new information for the regulation of bone metabolic diseases.

Therapeutic Effects of Berberine in Metabolic Diseases and Diabetes Mellitus

2021 ◽  
Author(s):  
Aram Khashayar ◽  
Zahra Bahari ◽  
Moradipour Elliyeh ◽  
Maedeh Ghasemi
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Diseases ◽  
Therapeutic Effects

scholarly journals Evaluation of Juniperus communis L. seed extract on benign prostatic hyperplasia induced in male Wistar rats

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Fatemeh Akbari ◽  
Mohammad Azadbakht ◽  
Kanu Megha ◽  
Ayat Dashti ◽  
Lale Vahedi ◽  
...  
Keyword(s):  
Benign Prostatic Hyperplasia ◽  
Wistar Rats ◽  
Histopathological Examination ◽  
Seed Extract ◽  
Prostatic Hyperplasia ◽  
Vehicle Group ◽  
Common Disease ◽  
Therapeutic Effects ◽  
Juniperus Communis ◽  
Male Wistar Rats

Abstract Background Benign prostatic hyperplasia (BPH) is a common disease which causes various health problems for elderly men such as urinary retention, recurring urinary tract infection and bladder stones. The aim of this study is to evaluate the therapeutic effects of Juniperus communis L. seed extract (JCS) on BPH in male Wistar rats. Methods To this end, 30 rats were divided into 5 groups (N = 6): group 1 (vehicle), group 2 (disease control), group 3 (standard medicine; 10 mg/kg finasteride), and groups 4 and 5 were treated with 300 mg/kg and 600 mg/kg of the hydroalcoholic JCS seed extract, respectively. Groups 2, 3, 4 and 5 received testosterone enanthate to induce prostatic hyperplasia. At the end of experimental period (28 days), prostate glands were cut off under anesthesia. Histopathological examination was done and biochemical parameters such as Malondialdehyde, Glutathione and protein carbonyl were also measured. Their body weights were also observed during the study. At the end of the experiment, prostate weights and prostate specific antigen (PSA) levels were measured. Prostate index, inhibition prostate weight and inhibition prostate index were also calculated. Results Both histopathological examination and biochemical parameter results showed significant improvements in rats treated with finasteride and 600 mg/kg JCS extract (p < 0.01). In addition, PSA levels showed significant decrease in comparison with the disease group. But acute toxicity test indicated that using JCS extract resulted in an increase in liver enzymes (ALP, LDH, SGOT, SGPT). As a result, the extract should be used with caution. Conclusions Oral administration of JCS extract is effective on preventing testosterone-induced benign prostatic hyperplasia.

scholarly journals N-Acetyl Cysteine Overdose Inducing Hepatic Steatosis and Systemic Inflammation in Both Propacetamol-Induced Hepatotoxic and Normal Mice

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 442
Author(s):  
Gunn-Guang Liou ◽  
Cheng-Chi Hsieh ◽  
Yi-Ju Lee ◽  
Pin-Hung Li ◽  
Ming-Shiun Tsai ◽  
...  
Keyword(s):  
Inbred Mouse ◽  
Serum Triglyceride ◽  
Mouse Strains ◽  
High Dose ◽  
Therapeutic Effects ◽  
Protein Nitration ◽  
Cholesterol Levels ◽  
Antioxidative Enzyme Activities ◽  
Acetyl Cysteine ◽  
Dose Dependent

Acetaminophen (APAP) overdose induces acute liver damage and even death. The standard therapeutic dose of N-acetyl cysteine (NAC) cannot be applied to every patient, especially those with high-dose APAP poisoning. There is insufficient evidence to prove that increasing NAC dose can treat patients who failed in standard treatment. This study explores the toxicity of NAC overdose in both APAP poisoning and normal mice. Two inbred mouse strains with different sensitivities to propacetamol-induced hepatotoxicity (PIH) were treated with different NAC doses. NAC therapy decreased PIH by reducing lipid oxidation, protein nitration and inflammation, and increasing glutathione (GSH) levels and antioxidative enzyme activities. However, the therapeutic effects of NAC on PIH were dose-dependent from 125 (N125) to 275 mg/kg (N275). Elevated doses of NAC (400 and 800 mg/kg, N400 and N800) caused additional deaths in both propacetamol-treated and normal mice. N800 treatments significantly decreased hepatic GSH levels and induced inflammatory cytokines and hepatic microvesicular steatosis in both propacetamol-treated and normal mice. Furthermore, both N275 and N400 treatments decreased serum triglyceride (TG) and induced hepatic TG, whereas N800 treatment significantly increased interleukin-6, hepatic TG, and total cholesterol levels. In conclusion, NAC overdose induces hepatic and systemic inflammations and interferes with fatty acid metabolism.

Effects of α-adrenoceptor agonists and antagonists on thyroid hormone secretion

1985 ◽  
Vol 108 (2) ◽  
pp. 184-191 ◽  
Author(s):  
Bo Ahrén
Keyword(s):  
Thyroid Hormone ◽  
Dose Level ◽  
Hormone Secretion ◽  
High Dose ◽  
Inhibitory Effects ◽  
High Dose Level ◽  
Adrenoceptor Antagonist ◽  
Adrenoceptor Agonist ◽  
Adrenoceptor Agonists

Abstract. The effects of various α-adrenoceptor agonists and antagonists on blood radioiodine levels were studied in mice pre-treated with 125I and thyroxine. The non-selective α-adrenoceptor agonist noradrenaline and the selective α1-adrenoceptor agonist phenylephrine both enhanced blood radioiodine levels. Noradrenaline was more potent than phenylephrine. Contrary, the selective α2-adrenoceptor agonist clonidine depressed basal levels of blood radioiodine. The non-selective α-adrenoceptor antagonist phentolamine and the selective α1-adrenoceptor antagonist prazosin both inhibited the noradrenaline-induced elevation of radioiodine levels, whereas the α2-adrenoceptor antagonist yohimbine had no such effect, except at a high dose level. All three α-adrenoceptor agonists, noradrenaline, phenylephrine and clonidine, inhibited the radioiodine response to TSH. In addition, TSH-induced increase in radioiodine levels was inhibited by prazosin, whereas yohimbine had no effect. Phentolamine inhibited the radioiodine response to TSH when given 2 h prior to TSH, whereas when given 15 min prior to TSH the response to TSH was potentiated by Phentolamine. It is concluded, that under in vivo conditions in the mouse, α1-adrenoceptor activation stimulates basal thyroid hormone secretion and inhibits TSH-induced thyroid hormone secretion. Further, α2-adrenoceptor activation inhibits basal thyroid hormone secretion. In addition, TSH-induced thyroid hormone secretion is inhibited by α1-adrenoceptor antagonism. Thus, α-adrenoceptors induce both stimulatory and inhibitory effects of thyroid function.

scholarly journals Quantitation, Absorption and Tissue Distribution of Coenzyme Q10 from Pak-wanban (Sauropus androgynus L. Merr.) Leaf and Its Antioxidant Activities

2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Aikkarach KETTAWAN ◽  
Kansuda WUNJUNTUK
Keyword(s):  
Tissue Distribution ◽  
Coenzyme Q10 ◽  
Antioxidant Activities ◽  
Alpha Tocopherol ◽  
Control Group ◽  
High Dose ◽  
Cooking Oil ◽  
Supplement Group ◽  
Male Wistar Rats ◽  
Plasma Antioxidant

Pak-wanban (Sauropus androgynus L. Merr.), a popular Thai vegetable, has been found to have a high content of Coenzyme Q10 (CoQ10), which is a powerful antioxidant. This study investigated the quantitation, absorption and tissue distribution of CoQ10 from raw and stir-fried Pak-wanban and its antioxidant activities in rats. Male Wistar rats (seven weeks old) were randomly grouped as follows: (1) control, (2) raw Pak-wanban powder of 0.5 mg CoQ10/kg/day, (3) stir-fried Pak-wanban powder of 0.5 mg CoQ10/kg/day, (4) stir-fried Pak-wanban powder of 1.0 mg CoQ10/kg/day, and (5) commercially CoQ10 supplement groups of 0.5 mg CoQ10/kg/day. The results found that stir-fried cooking did not significantly reduce the content of CoQ10 in the Pak-wanban leaves. After 3 weeks of experimentation, the level of CoQ10 in the plasma, liver and spleen was increased in all Pak-wanban groups when compared to the control group. The level of CoQ10 in the stir-fried Pak-wanban group was significantly higher than the raw Pak-wanban group but slightly lower than the CoQ10 supplement group.  Liver alpha-tocopherol concentrations were markedly increased in rats that consumed a high dose of CoQ10 from stir-fried Pak-wanban of 1 mg of CoQ10/kg/day when compared with the control group. Plasma antioxidant activities (ORAC: FRAP: DPPH) were significantly increased in both groups of stir-fried Pak-wanban when compared with the control group. We concluded that CoQ10 in  Pak-wanban could be well absorbed and improved the plasma antioxidant activities. Furthermore, cooking oil may increase the bioavailability of CoQ10 from vegetables. Therefore, it would be useful for vegetarian people.

Phase I Study of a Weekly Schedule of Irinotecan, High-Dose Leucovorin, and Infusional Fluorouracil as First-Line Chemotherapy in Patients With Advanced Colorectal Cancer

1999 ◽  
Vol 17 (3) ◽  
pp. 907-907 ◽  
Author(s):  
Udo Vanhoefer ◽  
Andreas Harstrick ◽  
Claus-Henning Köhne ◽  
Wolf Achterrath ◽  
Youcef M. Rustum ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Phase I ◽  
Dose Level ◽  
Phase I Study ◽  
Advanced Colorectal Cancer ◽  
High Dose ◽  
Weekly Schedule ◽  
First Line ◽  
Dose Levels ◽  
Line Chemotherapy

PURPOSE: To determine the maximum-tolerated dose (MTD) of a weekly schedule of irinotecan (CPT-11), leucovorin (LV), and a 24-hour infusion of fluorouracil (5-FU24h) as first-line chemotherapy in advanced colorectal cancer and to assess preliminary data on the antitumor activity. PATIENTS AND METHODS: Twenty-six patients with measurable metastatic colorectal cancer were entered onto this phase I study. In the first six dose levels, fixed doses of CPT-11 (80 mg/m2) and LV (500 mg/m2) in combination with escalated doses of 5-FU24h ranging from 1.8 to 2.6 g/m2 were administered on a weekly-times-four (dose levels 1 to 4) or weekly-times-six (dose levels 5 to 6) schedule. The dose of CPT-11 was then increased to 100 mg/m2 (dose level 7). RESULTS: Seventy-nine cycles of 5-FU24h/LV with CPT-11 were administered in an outpatient setting. No dose-limiting toxicities were observed during the first cycle at dose levels 1 to 6, but diarrhea of grade 4 (National Cancer Institute common toxicity criteria) was observed in three patients after multiple treatment cycles. Other nonhematologic and hematologic side effects, specifically alopecia and neutropenia, did not exceed grade 2. With the escalation of CPT-11 to 100 mg/m2 (dose level 7), diarrhea of grade 3 or higher was observed in four of six patients during the first cycle; thus, the MTD was achieved. Sixteen of 25 response-assessable patients (64%; 95% confidence interval, 45% to 83%) achieved an objective response. CONCLUSION: The recommended doses for further studies are CPT-11 80 mg/m2, LV 500 mg/m2, and 5-FU24h 2.6 g/m2 given on a weekly-times-six schedule followed by a 1-week rest period. The addition of CPT-11 to 5-FU24h/LV seems to improve the therapeutic efficacy in terms of tumor response with manageable toxicity.

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