Mechanistic Insights into the Pharmacological Significance of Silymarin

Molecules, Journal Year: 2022, Volume and Issue: 27(16), P. 5327 - 5327

Published: Aug. 21, 2022

Medicinal plants are considered the reservoir of diverse therapeutic agents and have been traditionally employed worldwide to heal various ailments for several decades. Silymarin is a plant-derived mixture polyphenolic flavonoids originating from fruits akenes Silybum marianum contains three flavonolignans, silibinins (silybins), silychristin silydianin, along with taxifolin. Silybins major constituents in silymarin almost 70–80% abundance accountable most observed activity. has also acknowledged ancient period utilized European Asian systems traditional medicine treating liver disorders. The contemporary literature reveals that significantly as neuroprotective, hepatoprotective, cardioprotective, antioxidant, anti-cancer, anti-diabetic, anti-viral, anti-hypertensive, immunomodulator, anti-inflammatory, photoprotective detoxification agent by targeting cellular molecular pathways, including MAPK, mTOR, β-catenin Akt, different receptors growth factors, well inhibiting numerous enzymes gene expression apoptotic proteins inflammatory cytokines. Therefore, current review aims recapitulate update existing knowledge regarding pharmacological potential evidenced vast cellular, animal, clinical studies, particular emphasis on its mechanisms action.

Language: Английский

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Role of Silymarin in Cancer Treatment: Facts, Hypotheses, and Questions

Journal of Evidence-Based Integrative Medicine, Journal Year: 2022, Volume and Issue: 27

Published: Jan. 1, 2022

The flavonoid silymarin extracted from the seeds of Sylibum marianum is a mixture 6 flavolignan isomers. 3 more important isomers are silybin (or silibinin), silydianin, and silychristin. Silybin functionally most active these compounds. This group flavonoids has been extensively studied they have used as hepato-protective substances for mushroom Amanita phalloides intoxication mainly chronic liver diseases such alcoholic cirrhosis nonalcoholic fatty liver. Hepatitis C progression not, or slightly, modified by silymarin. Recently, it also proposed SARS COVID-19 infection therapy. biochemical molecular mechanisms action in cancer subjects ongoing research. Paradoxically, many its identified actions antioxidant, promoter ribosomal synthesis, mitochondrial membrane stabilization, may seem protumoral at first sight, however, compounds clear anticancer effects. Some them are: decreasing migration through multiple targeting, hypoxia inducible factor-1α expression, inducing apoptosis some malignant cells, inhibiting promitotic signaling among others. Interestingly, antitumoral activity limited to cells while nonmalignant not be affected. Furthermore, there long history use human without toxicity after prolonged administration. ample distribution easy accessibility milk thistle—the source compounds, over counter availability, fact that weed, controversial issues regarding bioavailability, being nutraceutical rather than drug, somehow led medical professionals view effects with skepticism. fundamental reason why never achieved bedside status treatment. However, spite all effects, actually dual cases pancreatic can promote stemness. review deals recent investigations elucidate this cancer, consider possibility repurposing it. Particular attention dedicated silymarin's role controversies real effectiveness.

Language: Английский

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Silymarin and Inflammation: Food for Thoughts

Antioxidants, Journal Year: 2024, Volume and Issue: 13(1), P. 98 - 98

Published: Jan. 14, 2024

Inflammation is a vital defense mechanism, creating hostile conditions for pathogens, preventing the spread of tissue infection and repairing damaged tissues in humans animals. However, when inflammation resolution delayed or compromised as result its misregulation, process proceeds from acute phase to chronic inflammation, leading development various illnesses. It proven that redox balance disturbances oxidative stress are among major factors inducing NF-κB over-inflammation. Therefore, anti-inflammatory properties natural antioxidants have been widely tested vitro vivo systems. Accumulating evidence indicates silymarin (SM) main constituent silibinin/silybin (SB) great potential an anti-inflammation agent. The mechanism SM/SB action attributed inhibition TLR4/NF-κB-mediated signaling pathways downregulated expression pro-inflammatory mediators, including TNF-α, IL-1β, IL-6, IL-12, IL-23, CCL4, CXCL10, etc. Of note, same model systems, was able upregulate cytokines (IL-4, IL-10, IL-13, TGF-β, etc.) lipid mediators involved inflammation. inflammatory were clearly demonstrated systems based on immune (macrophages monocytes) non-immune (epithelial, skin, bone, connective cancer) cells. At time, confirmed number models, toxicity nonalcoholic fatty liver disease, ischemia/reperfusion stress-induced injuries, ageing exercising wound healing many other relevant seems likely activities key elements health-promoting these phytochemicals.

Language: Английский

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Investigation of the effects of hesperidin administration on abamectin‐induced testicular toxicity in rats through oxidative stress, endoplasmic reticulum stress, inflammation, apoptosis, autophagy, and JAK2/STAT3 pathways

Environmental Toxicology, Journal Year: 2021, Volume and Issue: 37(3), P. 401 - 412

Published: Nov. 8, 2021

In this study, the potential effects of hesperidin (HES) on chronic toxicity caused by abamectin (ABM) in testicular tissue were investigated through oxidative stress, inflammation, endoplasmic reticulum stress (ERS), apoptosis, and autophagy pathways. Male Sprague Dawley rats used study. Animals ABM group orally administered 1 mg/kg every other day for 28 days, while HES against was given at 100 or 200 30 min after administration days. Markers ERS, tissues removed animals are sacrificed analyzed using biochemical, real-time polymerase chain reaction (RT-PCR), western blot techniques. The results obtained showed that triggered autophagy. On hand, antioxidant effect increasing superoxide dismutase, catalase, glutathione peroxidase enzyme activities, levels testis attenuated lipid peroxidation. Accordingly, MAPK14 reduced NF-κB, IL-1β, TNF-α, IL-6 expression levels, presenting an anti-inflammatory effect. addition, Bax protected apoptosis reducing caspase-3, beclin-1, LC3A, LC3B expressions, Bcl-2 expression. It observed also interrupted JAK2/STAT3 signaling pathway suppressing Taken into consideration together, provided significant protection destruction with antioxidant, anti-inflammatory, antiapoptotic, anti-autophagic effects. Thus, it revealed has to serve as alternative treatment option toxicity.

Language: Английский

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The protective effects of hesperidin against paclitaxel-induced peripheral neuropathy in rats

Life Sciences, Journal Year: 2021, Volume and Issue: 287, P. 120104 - 120104

Published: Nov. 1, 2021

Language: Английский

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Chemopreventive effects of hesperidin against paclitaxel-induced hepatotoxicity and nephrotoxicity via amendment of Nrf2/HO-1 and caspase-3/Bax/Bcl-2 signaling pathways

Chemico-Biological Interactions, Journal Year: 2022, Volume and Issue: 365, P. 110073 - 110073

Published: July 31, 2022

Language: Английский

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Evaluation of protective effects of quercetin against cypermethrin‐induced lung toxicity in rats via oxidative stress, inflammation, apoptosis, autophagy, and endoplasmic reticulum stress pathway

Environmental Toxicology, Journal Year: 2022, Volume and Issue: 37(11), P. 2639 - 2650

Published: July 25, 2022

Cypermethrin (CYP), a type II synthetic pyrethroid, is the most widely used insecticide worldwide. Inhalation of it may cause side effects. This study aimed to examine potential protection quercetin (QUE) which well-known antioxidant in CYP-induced lung toxicity. Accordingly, 35 Spraque Dawley male rats were divided into five equal groups as follows: I-Control group, II-QUE group (50 mg/kg/b.w. QUE), III-CYP (25 CYP), IV-CYP + QUE 25 CYP V-CYP 50 QUE) treated with oral gavage throughout 28 days. intoxication was associated increased malondialdehyde level while glutathione concentration, activities peroxidase, superoxide dismutase, and catalase reduced. adminisitration caused apoptosis by up-regulating caspase-3 Bax levels down-regulating Bcl-2. also endoplasmic reticulum (ER) stress increasing mRNA transcript PERK, IRE1, ATF6, GRP78. Additionally, observed that administration activated IL-6/JAK2/STAT3/MAPK14 signaling pathway IL-1β, NF-κB, TNF-α, iNOS tissue. Therefore, determined triggered autophagy upregulating LC3A LC3B levels. Moreover, protein caspase-3, Bax, Bcl-2, cytochorme-c examined Western blot analysis. However, co-treatment at dose mg/kg considerably protective oxidative stress, inflammation, apoptosis, ER autophagy, Overall, findings this suggest damage toxicity could be protected administration.

Language: Английский

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A systematic review of the protective effects of silymarin/silibinin against doxorubicin-induced cardiotoxicity

Cancer Cell International, Journal Year: 2023, Volume and Issue: 23(1)

Published: May 10, 2023

Abstract Purpose Although doxorubicin chemotherapy is commonly applied for treating different malignant tumors, cardiotoxicity induced by this chemotherapeutic agent restricts its clinical use. The use of silymarin/silibinin may mitigate the doxorubicin-induced cardiac adverse effects. For aim, potential cardioprotective effects against were systematically reviewed. Methods In study, we performed a systematic search in accordance with PRISMA guideline identifying all relevant studies on “the role cardiotoxicity” electronic databases up to June 2022. Sixty-one articles obtained and screened based predefined inclusion exclusion criteria. Thirteen eligible papers finally included review. Results According echocardiographic electrocardiographic findings, doxorubicin-treated groups presented significant reduction ejection fraction, tissue Doppler peak mitral annulus systolic velocity, fractional shortening as well bradycardia, prolongation QT QRS interval. However, these abnormalities obviously improved silymarin plus groups. As well, administration led induce histopathological biochemical changes cells/tissue; contrast, co-administration could alterations (for most cases). Conclusion it was found that alleviates Silymarin/silibinin exerts via antioxidant, anti-inflammatory, anti-apoptotic activities, other mechanisms.

Language: Английский

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Impact of NQO1 dysregulation in CNS disorders

Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)

Published: Jan. 2, 2024

NAD(P)H Quinone Dehydrogenase 1 (NQO1) plays a pivotal role in the regulation of neuronal function and synaptic plasticity, cellular adaptation to oxidative stress, neuroinflammatory degenerative processes, tumorigenesis central nervous system (CNS). Impairment NQO1 activity CNS can result abnormal neurotransmitter release clearance, increased aggravated injury/death. Furthermore, it cause disturbances neural circuit neurotransmission. The abnormalities enzyme have been linked pathophysiological mechanisms multiple neurological disorders, including Parkinson's disease, Alzheimer's epilepsy, sclerosis, cerebrovascular traumatic brain injury, malignancy. contributes various dimensions treatment response tumors. precise through which contribute these disorders continue be subject ongoing research. Building upon existing knowledge, present study reviews current investigations describing dysregulations disorders. This emphasizes potential as biomarker diagnostic prognostic approaches, well its suitability target for drug development strategies

Language: Английский

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Oxidative stress: an overview of past research and future insights

All Life, Journal Year: 2024, Volume and Issue: 17(1)

Published: Feb. 21, 2024

'Oxidative stress' (OS) refers to the deviations in redox biology inside biological systems. This term has been used illustrate imbalance between oxidants and antioxidants, which a subject of extensive research. The obtained findings suggest that many diseases are linked OS, including diabetes mellitusinflammation, cancers, autoimmune disorders neurodegenerative diseases. More recently, significant advances biochemistry molecular have enabled researchers find master switches various OS mechanisms associate development paradigms. In this review, brief overview research is provided offer insight into its future directions. Most importantly, need for greater understanding vital role progression emphasized. Likewise, more work needed on utility reactive oxygen species markers as diagnostic tool.

Language: Английский

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