Prophylactic effect of &lt;i&gt;Withania somnifera&lt;/i&gt; on inflammation in a non-autoimmune prone murine model of lupus

Minhas, Ujla; Minz, Ranjana W.; Bhatnagar, Archana

doi:10.5582/ddt.2011.v5.4.195

Cited by 21 publications

(10 citation statements)

References 22 publications

(23 reference statements)

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“…for review) contributing to mitochondrial function and inducing cell death. In this regard, it has widely reported that Wse show a potent inhibitory effect on inflammatory markers such as ROS in a mouse model of lupus4647. Interestingly Wse reduced rotenone-induced oxidative impairment and mitochondrial respiratory chain enzymes and such impairments were responsible for reduced locomotor deficits and lethality in a Drosophila melanogaster model of Parkinson induced by rotenone, a naturally occurring common pesticide which specifically inhibits mitochondrial complex-I activity48.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of phytotherapic preparations in the hSOD1 Drosophila melanogaster model of ALS

Rose

Talani

Catelani

et al. 2017

Sci Rep

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The present study was aimed at characterizing the effects of Withania somnifera (Wse) and Mucuna pruriens (Mpe) on a Drosophila melanogaster model for Amyotrophic Lateral Sclerosis (ALS). In particular, the effects of Wse and Mpe were assessed following feeding the flies selectively overexpressing the wild human copper, zinc-superoxide dismutase (hSOD1-gain-of-function) in Drosophila motoneurons. Although ALS-hSOD1 mutants showed no impairment in life span, with respect to GAL4 controls, the results revealed impairment of climbing behaviour, muscle electrophysiological parameters (latency and amplitude of ePSPs) as well as thoracic ganglia mitochondrial functions. Interestingly, Wse treatment significantly increased lifespan of hSDO1 while Mpe had not effect. Conversely, both Wse and Mpe significantly rescued climbing impairment, and also latency and amplitude of ePSPs as well as failure responses to high frequency DLM stimulation. Finally, mitochondrial alterations were any more present in Wse- but not in Mpe-treated hSOD1 mutants. Hence, given the role of inflammation in the development of ALS, the high translational impact of the model, the known anti-inflammatory properties of these extracts, and the viability of their clinical use, these results suggest that the application of Wse and Mpe might represent a valuable pharmacological strategy to counteract the progression of ALS and related symptoms.

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Section: Discussionmentioning

confidence: 99%

Differential effects of phytotherapic preparations in the hSOD1 Drosophila melanogaster model of ALS

Rose

Talani

Catelani

et al. 2017

Sci Rep

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“…The prophylactic effects of WS extract were characterized by orally administering WS for one month prior and six months following pristane injections. WS treatment resulted in significant reductions in ROS formation within intraperitoneal macrophages, as well as reductions in inflammatory cytokines (IL-6 and TNF-α), and decreased inflammation within the kidneys, liver, and lung, however, no reduction in the humoral response autoantibodies or immune complex deposition [180,181].…”

Section: Therapeutic Benefits Of Withanolides For Sle and Ibd In Vivomentioning

confidence: 97%

Natural Withanolides in the Treatment of Chronic Diseases

White

Subramanian

Motiwala

et al. 2016

Advances in Experimental Medicine and Biology

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Withanolides, and in particular extracts from Withania somnifera, have been used for over 3,000 years in traditional Ayurvedic and Unani Indian medical systems as well as within several other Asian countries. Traditionally, the extracts were ascribed a wide range of pharmacologic properties with corresponding medical uses, including adaptogenic, diuretic, anti-inflammatory, sedative/anxiolytic, cytotoxic, antitussive, and immunomodulatory. Since the discovery of the archetype withaferin A in 1965, approximately 900 of these naturally occurring, polyoxygenated steroidal lactones with 28-carbon ergostane skeletons have been discovered across 24 diverse structural types. Subsequently, extensive pharmacologic research has identified multiple mechanisms of action across key inflammatory pathways. In this chapter we identify and describe the major withanolides with anti-inflammatory properties, illustrate their role within essential and supportive inflammatory pathways (including NF-κB, JAK/STAT, AP-1, PPARγ, Hsp90 Nrf2, and HIF-1), and then discuss the clinical application of these withanolides in inflammation-mediated chronic diseases (including arthritis, autoimmune, cancer, neurodegenerative, and neurobehavioral). These naturally derived compounds exhibit remarkable biologic activity across these complex disease processes, while showing minimal adverse effects. As novel compounds and analogs continue to be discovered, characterized, and clinically evaluated, the interest in withanolides as a novel therapeutic only continues to grow.

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“…Reactive oxygen species (ROS) play a major pathogenic role in a wide range of types of human [1] and experimental [2], [3] glomerulonephritis, including IgA nephropathy (IgAN) [4]–[7]. Importantly, in both patients [4], [5], [8] and animal models [7], [9], [10], ROS have been shown to be involved in the progressive stage of IgAN, the most common type of primary glomerulonephritis.…”

Section: Introductionmentioning

confidence: 99%

Osthole Mitigates Progressive IgA Nephropathy by Inhibiting Reactive Oxygen Species Generation and NF-κB/NLRP3 Pathway

et al. 2013

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Renal reactive oxygen species (ROS) and mononuclear leukocyte infiltration are involved in the progressive stage (exacerbation) of IgA nephropathy (IgAN), which is characterized by glomerular proliferation and renal inflammation. The identification of the mechanism responsible for this critical stage of IgAN and the development of a therapeutic strategy remain a challenge. Osthole is a pure compound isolated from Cnidiummonnieri (L.) Cusson seeds, which are used as a traditional Chinese medicine, and is anti-inflammatory, anti-apoptotic, and anti-fibrotic both in vitro and in vivo. Recently, we showed that osthole acts as an anti-inflammatory agent by reducing nuclear factor-kappa B (NF-κB) activation in and ROS release by activated macrophages. In this study, we examined whether osthole could prevent the progression of IgAN using a progressive IgAN (Prg-IgAN) model in mice. Our results showed that osthole administration resulted in prevention of albuminuria, improved renal function, and blocking of renal progressive lesions, including glomerular proliferation, glomerular sclerosis, and periglomerular mononuclear leukocyte infiltration. These findings were associated with (1) reduced renal superoxide anion levels and increased Nrf2 nuclear translocation, (2) inhibited renal activation of NF-κB and the NLRP3 inflammasome, (3) decreased renal MCP-1 expression and mononuclear leukocyte infiltration, (4) inhibited ROS production and NLRP3 inflammasome activation in cultured, activated macrophages, and (5) inhibited ROS production and MCP-1 protein levels in cultured, activated mesangial cells. The results suggest that osthole exerts its reno-protective effects on the progression of IgAN by inhibiting ROS production and activation of NF-κB and the NLRP3 inflammasome in the kidney. Our data also confirm that ROS generation and activation of NF-κB and the NLRP3 inflammasome are crucial mechanistic events involved in the progression of the renal disorder.

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Prophylactic effect of <i>Withania somnifera</i> on inflammation in a non-autoimmune prone murine model of lupus

Cited by 21 publications

References 22 publications

Differential effects of phytotherapic preparations in the hSOD1 Drosophila melanogaster model of ALS

Differential effects of phytotherapic preparations in the hSOD1 Drosophila melanogaster model of ALS

Natural Withanolides in the Treatment of Chronic Diseases

Osthole Mitigates Progressive IgA Nephropathy by Inhibiting Reactive Oxygen Species Generation and NF-κB/NLRP3 Pathway

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