Cordycepin Modulates Body Weight by Reducing Prolactin Via an Adenosine A1 Receptor

Background: Cordycepin is an extract from the insect fungus Cordyceps. militaris with various biological function. In previous studies, cordycepin has demonstrated an excellent anti-obesity effect, but the mechanism is unclear. It was also demonstrated that prolactin played an important role in body weight regulation and hyperprolactinemia can promote appetite and accelerate fat deposition. In this study, we explored the molecular mechanism of the anti-obesity effect of cordycepin. Methods: In Vivo, the obese rat model was induced by high fat diet for five weeks, and the serum and liver lipid levels coupled with the serum prolactin levels were reduced following cordycepin treatment (P<0.01). Results: The results suggested that cordycepin is a potential drug that lowers blood and liver lipid levels and reduces body weight related to prolactin. Cordycepin also protects adipocytes from enlargement and hepatocytes from lipotoxicity-induced inflammation. In vitro, cordycepin inhibited prolactin secretion in GH3 cells via upregulating the expression of adenosine A1 receptor, and the inhibition effect was blocked by an antagonist of adenosine receptor A1 DPDPX, demonstrating that cordycepin may work as an adenosine agonist. Additionally, cordycepin inhibited the ERK/AKT/PI3K pathway in GH3 cells. At the same time, cordycepin blocked prolactininduced upregulation of lipogenesis genes PRLR, and phosphorylation of JAK2 in 3T3-L1 cells. In an in vivo study, cordycepin downregulated the expression of prolactin receptor (PRLR) but not the phosphorylation of JAK2. Conclusion: Thus, it was proved that cordycepin modulates body weight by reducing prolactin release via an adenosine A1 receptor.

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Cordycepin Modulate Body Weight by Reducing Prolactin via an Adenosine A1 Receptor

10.20944/preprints201804.0033.v1 ◽

2018 ◽

Cited By ~ 1

Author(s):

Yuan Li ◽

Yan Li ◽

Xueyan Wang ◽

Hongyue Xu ◽

Chao Wang ◽

...

Keyword(s):

Body Weight ◽

Prolactin Secretion ◽

Adenosine A1 Receptor ◽

Gh3 Cells ◽

Serum Prolactin ◽

Prolactin Release ◽

Adenosine A1 ◽

A1 Receptor

Cordycepin is an extract from the insect fungus Cordyceps. militaris, which is a traditional medicine with various biological function. In previous studies, cordycepin had been reported with excellent anti-obesity effect, but the mechanism is unclear. A large quantity of evidences showed that prolactin plays an important part in body weight regulation, hyperprolactinemia can promote appetite and accelerate fat deposition. In this study, we explored the molecular mechanism of the anti-obesity effect of cordycepin by reducing prolactin release via an adenosine A1 receptor. In vivo, obese rats model was induced by high fat diet for 5 weeks, the serum and liver lipids coupling with serum prolactin were reduced by treatment of cordycepin, the results suggested that cordycepin is a potential drug for therapying obesity which could be related with prolactin. In vitro, cordycepin could inhibit prolactin secretion in GH3 cells via upregulating the expression of adenosine A1 receptor, the inhibition effect could be blocked by an antagonist of adenosine receptor A1 DPDPX, prolactin induced the upregulation of lipogenesis genes PRLR, and P-JAK2 in 3T3-L1 cells. Intriguingly, cordycepin would down-regulate the expression of prolactin receptor (PRLR). Thus, we concluded that cordycepin modulate body weight by reducing prolactin release via an adenosine A1 receptor.

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Deletion of the adenosine A1 receptor gene does not alter neuronal damage following ischaemia in vivo or in vitro

European Journal of Neuroscience ◽

10.1111/j.1460-9568.2004.03564.x ◽

2004 ◽

Vol 20 (5) ◽

pp. 1197-1204 ◽

Cited By ~ 36

Author(s):

Tomas Olsson ◽

Tobias Cronberg ◽

Anna Rytter ◽

Fredrik Asztely ◽

Bertil B. Fredholm ◽

...

Keyword(s):

Neuronal Damage ◽

Receptor Gene ◽

Adenosine A1 Receptor ◽

Adenosine A1 ◽

A1 Receptor

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Chronic theophylline treatment in vivo increases high affinity adenosine A1 receptor binding and sensitivity to exogenous adenosine in the in vitro hippocampal slice

Brain Research ◽

10.1016/0006-8993(91)90997-a ◽

1991 ◽

Vol 542 (1) ◽

pp. 55-62 ◽

Cited By ~ 17

Author(s):

Carl R. Lupica ◽

Michael F. Jarvis ◽

Robert F. Berman

Keyword(s):

Receptor Binding ◽

Hippocampal Slice ◽

Adenosine A1 Receptor ◽

High Affinity ◽

Adenosine A1 ◽

A1 Receptor

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The in vivo respiratory phenotype of the adenosine A1 receptor knockout mouse

Respiratory Physiology & Neurobiology ◽

10.1016/j.resp.2015.11.005 ◽

2016 ◽

Vol 222 ◽

pp. 16-28 ◽

Cited By ~ 2

Author(s):

Dirk Heitzmann ◽

Philipp Buehler ◽

Frank Schweda ◽

Michael Georgieff ◽

Richard Warth ◽

...

Keyword(s):

Knockout Mouse ◽

Adenosine A1 Receptor ◽

Receptor Knockout Mouse ◽

Adenosine A1 ◽

A1 Receptor

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Adenosine A1 receptor-mediated inhibition of in vitro prolactin secretion from the rat anterior pituitary

Brazilian Journal of Medical and Biological Research ◽

10.1590/s0100-879x2006001100013 ◽

2006 ◽

Vol 39 (11) ◽

Cited By ~ 1

Author(s):

D.L.W. Picanço-Diniz ◽

M.M. Valença ◽

J. Antunes-Rodrigues

Keyword(s):

Anterior Pituitary ◽

Prolactin Secretion ◽

Adenosine A1 Receptor ◽

Adenosine A1 ◽

A1 Receptor

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Regulation of Na(+)-3HCO3- cotransport in rabbit proximal convoluted tubule via adenosine A1 receptor

AJP Renal Physiology ◽

10.1152/ajprenal.1993.265.4.f511 ◽

1993 ◽

Vol 265 (4) ◽

pp. F511-F519 ◽

Cited By ~ 14

Author(s):

M. Takeda ◽

K. Yoshitomi ◽

M. Imai

Keyword(s):

Basolateral Membrane ◽

Receptor Activation ◽

Proximal Convoluted Tubule ◽

Adenosine A1 Receptor ◽

Intracellular Camp ◽

Dependent Manner ◽

Concentration Dependent Manner ◽

Adenosine A1 ◽

A1 Receptor

We investigated the role of adenosine A1-receptor in the regulation of basolateral Na(+)-3HCO3- cotransporter in the rabbit proximal convoluted tubule (PCT) microperfused in vitro by monitoring basolateral membrane potential and intracellular pH. FK-453, a highly specific A1 antagonist, inhibited basolateral HCO3- conductance in a concentration-dependent manner (10(-10)-10(-5) M). Other A1 antagonists, 8-cyclopentyl-1,3-dipropylxanthine (DPCPX) at 10(-5) M and theophylline at 10(-3) M, also had similar effects. N6-cyclohexyladenosine (CHA) at 10(-7) M attenuated the effect of low concentration (10(-8) M) of FK-453. Either enhancement of the degradation of adenosine by 0.1 U/ml adenosine deaminase (ADA) or inhibition of adenosine release from the cells by 10(-6) M S-(4-nitrobenzyl)-6-thioinosine (NBTI) mimicked the effects of A1 antagonists. These observations suggest that endogenous adenosine is released from PCT cells and stimulates Na(+)-3HCO3- cotransporter. Both 10(-4) M 8-(4-chlorophenylthio)-adenosine 3',5'-cyclic monophosphate (CPT-cAMP) and 10(-6) M forskolin also inhibited basolateral HCO3- conductance. Both 10(-6) M FK-453 and 10(-4) M CPT-cAMP decreased the initial rate as well as the magnitude of intracellular acidification induced by reduction of peritubular HCO3- concentration from 25 to 0 mM. Neither 10(-6) M FK-453 nor 10(-7) M CHA changed intracellular Ca2+ concentration as measured by fura-2 fluorescence. These results indicate that adenosine might stimulate HCO3- exit across the basolateral membrane through Na(+)-3HCO3- cotransporter by decreasing intracellular cAMP via A1-receptor activation.(ABSTRACT TRUNCATED AT 250 WORDS)

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Enhancement of adenosine A1 receptor functions by benzoylthiophenes in guinea pig tissues in vitro

Naunyn-Schmiedeberg s Archives of Pharmacology ◽

10.1007/bf00176776 ◽

1995 ◽

Vol 352 (2) ◽

Cited By ~ 6

Author(s):

E. Leung ◽

L.K.M. Walsh ◽

L.A. Flippin ◽

E.J. Kim ◽

D.A. Lazar ◽

...

Keyword(s):

Guinea Pig ◽

Adenosine A1 Receptor ◽

Adenosine A1 ◽

A1 Receptor

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The p38 MAPK Inhibitor SB203580 Blocks Adenosine A1 Receptor-Induced Attenuation of In Vivo Myocardial Stunning

Cardiovascular Drugs and Therapy ◽

10.1007/s10557-004-6220-4 ◽

2004 ◽

Vol 18 (6) ◽

pp. 433-440 ◽

Cited By ~ 10

Author(s):

Yukihiro Yoshimura ◽

Gentian Kristo ◽

Byron J. Keith ◽

Salik A. Jahania ◽

Robert M. Mentzer ◽

...

Keyword(s):

P38 Mapk ◽

Myocardial Stunning ◽

Adenosine A1 Receptor ◽

Adenosine A1 ◽

A1 Receptor ◽

P38 Mapk Inhibitor ◽

Mapk Inhibitor

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Bauhiniastatin-1 alleviates diet induced obesity and lipid accumulation through modulating PPAR-γ/AMPK expressions: In-vitro, in-vivo and in-silico studies.

10.21203/rs.3.rs-302339/v1 ◽

2021 ◽

Author(s):

Karunakaran Reddy Sankaran ◽

Lokanatha Oruganti ◽

Muni Swamy Ganjayi ◽

Venkataramaiah Chintha ◽

Muni Kesavulu Muppuru ◽

...

Keyword(s):

Body Weight ◽

Weight Gain ◽

Western Blot ◽

Blot Analysis ◽

Body Weight Gain ◽

Liver Lipid ◽

Ppar Γ ◽

Diet Induced Obesity

Abstract Background: Consumption of energy dense foods and sedentary lifestyles have led to high prevalence of obesity and associated disorders. Intensive research efforts have focussed to develop effective alternative therapeutics from plant sources. Bauhiniastatins have been reported to possess antineoplastic activity. In the present study, Bauhiniastatin-1 (BSTN1) was isolated and purified from Bauhinia purpurea and evaluated for its therapeutic efficacy against adipogenesis and obesity using high fat diet (HFD)-induced obese rodent model and 3T3-L1 cells.Methods: We performed in-vitro experiments like MTT assay, Oil Red O (ORO) stain, cellular lipid content, glycerol release and RT-PCR analysis in 3T3-L1 cells. In-vivo parameters like body weight gain, body composition, plasma adipokines, serum & liver lipid profiles, liver marker enzymes, western blot analysis and histopathological examination were conducted in rat model. In addition, molecular docking studies were also performed to understand interaction of BSTN1 with peroxisome proliferator-activated gamma receptor (PPAR-γ) and AMP-activated protein kinase (AMPK) which supported our experimental results.Results: BSTN1 at 20 μM significantly (p<0.001) inhibited cell differentiation and lipid accumulation of 3T3-L1 adipocytes. Mechanistic studies showed that mRNA expression of key adipogenic markers, PPAR-γ, fatty acid synthase (FAS) and sterol-regulatory element-binding protein-1 (SREBP1) were down-regulated while AMPK was up-regulated by BSTN1. Oral administration of BSTN1 (5 mg/kg. b.wt.) to HFD-induced obese rats substantially decreased body weight gain, fat mass, serum and liver lipid levels and promoted integrity of hepatic and adipose tissue architecture compared to HFD-control rats. In BSTN1 administered groups, decreased serum aspartate transaminase (AST) and alanine aminotransferase (ALT) levels, decreased plasma leptin but increased adiponectin levels were noted. Western blot analysis of adipose and hepatic tissues collected from BSTN1 treated rats showed decreased expression level of PPAR-γ but increase in AMPK expression relative to the untreated group. In-silico studies showed strong binding interactions of BSTN1 against PPAR-γ and AMPK, the key molecules of adipogenesis and obesity.Conclusions: Taken together, the results suggest that BSTN1 could be promising molecule for the treatment of diet-induced obesity and non-alcoholic fatty liver disease (NAFLD).

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