Anti-inflammatory activity of Withania somnifera leaf extract in stainless steel implant induced inflammation in adult zebrafish

Sivamani, S.; Joseph, Benin; Kar, Bibhas

doi:10.1016/j.jgeb.2014.01.002

Cited by 39 publications

(17 citation statements)

References 24 publications

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“…NFkB activation and its translocation are critical for the expression of the various cytokines, chemokines, receptors required for neutrophil adhesion and migration, MHCs, iNOS, and COX-2 in microglia in response to LPS [ 44 , 45 ]. Our results are in line with the recent reports suggesting that anti-inflammatory activity of 30 % methanolic extract of the Withania leaves in stainless steel implant induced inflammation in zebrafish by inhibiting the NFkB transcriptional activity [ 46 ]. Further, its active component, i.e., Wit A has also been reported to inhibit the NFkB activity in cellular model of cystic fibrosis inflammation [ 47 ].…”

Section: Discussionsupporting

confidence: 93%

Aqueous extract from the Withania somnifera leaves as a potential anti-neuroinflammatory agent: a mechanistic study

Gupta

Kaur

2016

J Neuroinflammation

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BackgroundMicroglial-mediated neuroinflammation is a key factor underlying the pathogenesis of various neurodegenerative diseases and also an important target for the development of the neuroinflammation-targeted therapeutics. Conventionally, the nonsteroidal anti-inflammatory drugs (NSAIDs) are prescribed, but they are associated with long-term potential risks. Natural products are the cornerstone of modern therapeutics, and Ashwagandha is one such plant which is well known for its immunomodulatory properties in Ayurveda.MethodsThe current study was aimed to investigate the anti-neuroinflammatory potential of Ashwagandha (Withania somnifera) leaf water extract (ASH-WEX) and one of its active chloroform fraction (fraction IV (FIV)) using β-amyloid and lipopolysaccharide (LPS)-stimulated primary microglial cells and BV-2 microglial cell line. Iba-1 and α-tubulin immunocytochemistry was done to study the LPS- and β-amyloid-induced morphological changes in microglial cells. Inflammatory molecules (NFkB, AP1), oxidative stress proteins (HSP 70, mortalin), apoptotic markers (Bcl-xl, PARP), cell cycle regulatory proteins (PCNA, Cyclin D1), and MHC II expression were analyzed by Western blotting. Mitotracker and CellRox Staining, Sandwich ELISA, and Gelatin Zymography were done to investigate ROS, pro-inflammatory cytokines, and matrix metalloproteinase production, respectively. Ashwagandha effect on microglial proliferation, migration, and its apoptosis-inducing potential was studied by cell cycle analysis, migration assay, and Annexin-V FITC assay, respectively.ResultsASH-WEX and FIV pretreatment was seen to suppress the proliferation of activated microglia by causing cell cycle arrest at Go/G1 and G2/M phase along with decrease in cell cycle regulatory protein expression such as PCNA and Cyclin D1. Inhibition of microglial activation was revealed by their morphology and downregulated expression of microglial activation markers like MHC II and Iba-1. Both the extracts attenuated the TNF-α, IL-1β, IL-6, RNS, and ROS production via downregulating the expression of inflammatory proteins like NFkB and AP1. ASH-WEX and FIV also restricted the migration of activated microglia by downregulating metalloproteinase expression. Controlled proliferation rate was also accompanied by apoptosis of activated microglia. ASH-WEX and FIV were screened and found to possess Withaferin A and Withanone as active phytochemicals.ConclusionsThe current data suggests that ASH-WEX and FIV inhibit microglial activation and migration and may prove to be a potential therapeutic candidate for the suppression of neuroinflammation in the treatment of neurodegenerative diseases.

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Section: Discussionsupporting

confidence: 93%

Aqueous extract from the Withania somnifera leaves as a potential anti-neuroinflammatory agent: a mechanistic study

Gupta

Kaur

2016

J Neuroinflammation

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“…Therefore, we repeated HPLC for water but with 1.5dilution factor to allow the active compound appear as peaks in same retention time of Standard but in different area. These results agreed with [18] who's also found more than five types of flavonoids but in different concentrations. The concentrations of these flavonoids depend on the growth culture condition and the active compound extraction method.…”

Section: Showed Major Peaks With Different Retention Times and Area Osupporting

confidence: 91%

Antimicrobial and Cytotoxic Activity of Withania somnifera

Atta¹,

Al-Ani²

2015

JNUS

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Withania somnifera (L) Dunal popularly known as 'Ashwagandha' had been used in folk medicine. Ten grams of leaves powder were used to extract the active substances as water, ethanol, and acetone extracts. The extracts were subjected to chemical analysis to identify the active components, Alkaloids, Glycosides, Saponins, Flavonoids, Fixed oil was present in ethanol, acetone and water extracts while terpene was absent in water extract, Proteins were not found in acetone extract, Tannins were absent in all types of extracts. HPLC analysis revealed that all types of Withania extracts contained two types of Alkaloids (Withanolide-A and Withaferin-A), seven types of Flavonoids (Naringenin, Catechin, Luteolin, Hesperetin, Kaempfero, Apigenin and Naringin) and two types of Saponins (Sitoindosides VII and Sitoindosides VIII) appeared as different peaks in same retention times with standard. Withania extracts contained numbers of active group detected by FTIR. Antimicrobial activities for all types of extracts werecarried out against different types of bacteria and fungi but only Acetone extract showed antimicrobial activity on the fungus (Trichophyton violaceum). W. somnifera extracts had cytotoxic effect on HepG2 cell line, higher cytotoxic effect in ethanol extract appeared at 120 mg/ml concentration, Water extract was inbetween and acetone extract was the lowest one.

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“…Also, the anti-inflammatory activity of methanol:water (3:7) extract from the leaves of W . somnifera has been reported in stainless steel implant-induced inflammation in zebrafish [ 51 ]. The anti-inflammatory activity of the plant has been attributed to the rich concentration of flavonoids and phenolic acids such as rutin, gallic acid, quercetin, vanillic acid, and kaempferol in the TLC-separated portion of the supernatant of methanolic extract from the leaves of the plant [ 51 ].…”

Section: Discussionmentioning

confidence: 99%

Withania somnifera as a potential candidate to ameliorate high fat diet-induced anxiety and neuroinflammation

Kaur

2017

J Neuroinflammation

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BackgroundThe epidemic of obesity has reached alarming levels in both developing and developed nations. Excessive calorie intake and sedentary lifestyle due to technological advancements are the main causal factors for overweight and obesity among the human population. Obesity has been associated with a number of co-morbidities such as hypertension, type 2 diabetes mellitus, cardiovascular diseases, and neurodegeneration and dementia. The progression of neurological disorders in obese subjects has been mainly attributed to neuroinflammation. Withania somnifera has been used in numerous Ayurvedic formulations owing to its wide array of health-promoting properties. The current study was designed to test the hypothesis whether dry leaf powder of W. somnifera has anxiolytic and anti-neuroinflammatory potential in diet-induced obesity.MethodsYoung adult female rats were divided into four groups: low fat diet group (LFD) fed with regular chow feed, high fat diet group (HFD) fed with diet containing 30% fat by weight, low fat diet plus extract group (LFDE) fed with regular chow feed supplemented with dry leaf powder of W. somnifera 1 mg/g of body weight (ASH), and high fat diet plus extract group (HFDE) fed with diet containing 30% fat by weight and supplemented with ASH. All the animals were kept on respective feeding regimen for 12 weeks; following which, the animals were tested for their anxiety-like behavior using elevated plus maze test. The animals were sacrificed and used to study various inflammatory markers such as GFAP, Iba1, PPARγ, iNOS, MCP-1, TNFα, IL-1β, IL-6, and various markers of NF-κB pathway by Western blotting and quantitative real-time PCR. Serum levels of leptin, insulin and pro-inflammatory cytokines were also assayed.ResultsASH treated rats showed less anxiety levels as compared to HFD animals. At molecular level, ASH ameliorated the HFD-induced reactive gliosis and microgliosis and suppressed the expression of inflammatory markers such as PPARγ, iNOS, MCP-1, TNFα, IL-1β, and IL-6. Further, ASH ameliorated leptin and insulin resistance and prevented HFD-induced apoptosis.ConclusionsDry leaf powder of W. somnifera may prove to be a potential therapeutic agent to attenuate neuroinflammation associated with obesity and may prevent its co-morbidities.

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Anti-inflammatory activity of Withania somnifera leaf extract in stainless steel implant induced inflammation in adult zebrafish

Cited by 39 publications

References 24 publications

Aqueous extract from the Withania somnifera leaves as a potential anti-neuroinflammatory agent: a mechanistic study

Aqueous extract from the Withania somnifera leaves as a potential anti-neuroinflammatory agent: a mechanistic study

Antimicrobial and Cytotoxic Activity of Withania somnifera

Withania somnifera as a potential candidate to ameliorate high fat diet-induced anxiety and neuroinflammation

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