Hepatoprotective effects of extracts, fractions and compounds from the stem bark of Pentaclethra macrophylla Benth: Evidence from in vitro and in vivo studies

Bomgning, Cyrille Lionel Kamga; Ponou, Beaudelaire Kemvoufo; Fotio, Agathe Lambou; Tsague, Mathias Kenfack; Tsafack, Borice Tapondjou; Kühlborn, Jonas; Mbuyo-Nguelefack, Elvine Pami; Teponno, Rémy Bertrand; Opatz, Till; Tapondjou, Léon Azefack; Nguelefack, Télesphore Benoît

doi:10.1016/j.biopha.2021.111242

Cited by 9 publications

(5 citation statements)

References 25 publications

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“…Since GSH, as an essential co-substrate of glutathione peroxidase (GPX)4, contributes to the reduction of lipid hydroperoxides and prevents degenerative cell death 139 , we speculated that the decrease in GSH might enhance lipid peroxidation, which was, however, not the case (Figure 8I). Silybin actually attenuated the formation of lipid peroxidation products by trend in the liver but not in the kidney (Figure 8I), consistent with previous studies on silymarin/silybin 86,140,141 .…”

Section: Resultssupporting

confidence: 92%

Silybin A fromSilybum marianumreprograms lipid metabolism to induce a cell fate-dependent class switch from triglycerides to phospholipids

Koeberle,

Thürmer,

Werner

et al. 2024

Preprint

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Silybum marianumis used to protect against degenerative liver damage. The molecular mechanisms of its bioactive component, silybin, remained enigmatic, although membrane-stabilizing properties, modulation of membrane protein function, and metabolic regulation have been discussed for decades. Here, we show that specifically the stereoisomer silybin A decreases triglyceride levels and lipid droplet content, while enriching major phospholipid classes and maintaining a homeostatic phospholipid composition in human hepatocytesin vitroand in mouse liverin vivounder normal and pre-disease conditions. Conversely, in cell-based disease models of lipid overload and lipotoxic stress, silybin treatment primarily depletes triglycerides. Mechanistically, silymarin/silybin suppresses phospholipid-degrading enzymes, induces phospholipid biosynthesis to varying degrees depending on the conditions, and down-regulates triglyceride biosynthesis, while inducing complex changes in sterol and fatty acid metabolism. Structure-activity relationship studies highlight the importance of the 1,4-benzodioxane ring configuration of silybin A in triglyceride reduction and the saturated 2,3-bond of the flavanonol moiety in phospholipid accumulation. Enrichment of hepatic phospholipids and intracellular membrane expansion are associated with an heightened biotransformation capacity. In conclusion, our study deciphers the structural features of silybin contributing to hepatic lipid reorganization and offers insights into its liver-protective mechanism, potentially involving a context-dependent lipid class switch from triglycerides to phospholipids.

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Section: Resultssupporting

confidence: 92%

Silybin A fromSilybum marianumreprograms lipid metabolism to induce a cell fate-dependent class switch from triglycerides to phospholipids

Koeberle,

Thürmer,

Werner

et al. 2024

Preprint

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“…11‐ O ‐galloylbergenin (18) (IC 50 1.8 μg/mL). The ethylacetate fraction was the most effective fraction and reduced the serum level of ALAT, ASAT, and TNF‐α in vivo (Bomgning et al, 2021). The phytochemical analysis revealed the presence of alkaloids, flavonoids, steroids, glycosides, tannins, saponnins, terpenoids, reducing sugars, resins, and carbohydrates.…”

Section: Methods Of Study Designmentioning

confidence: 99%

Recent insights into the hepatoprotective potential of medicinal plants and plant‐derived compounds

Thilagavathi

Begum

Varatharaj

et al. 2023

Phytotherapy Research

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Liver problems are a worldwide concern, and conventional medicinal therapies are ineffective. Hence, safeguarding the healthy liver is vital for good health and well‐being. Infections due to virus, immune problems, cancer, alcohol abuse, and an overdose of drugs are some of the causes of liver diseases. Antioxidants derived from medicinal plants and conventional dietary sources can protect the liver from damages caused by oxidative stress system and various chemicals. Plants and plant‐derived phytochemicals are appealing hepatoprotective agents since they have less side effects and still there is a lot of interest shown in using herbal tonics for treating liver disorders. This review therefore primarily focuses on newly discovered medicinal plants and compounds produced from plants that fall under the classifications of flavonoids, alkaloids, terpenoids, polyphenolics, sterols, anthocyanins, and saponin glycosides, all of which have the potential to be hepatoprotective. Hosta plantaginea, Ligusticum chuanxiong, Daniella oliveri, Garcinia mangostana, Solanum melongena, Vaccinium myrtillus, Picrorhiza kurroa, and Citrus medica are some potential plants having hepatoprotective effects. We conclude that these phytochemicals and the plant extracts listed above are used in the future to treat a variety of liver diseases, additional research is still needed to develop safer and more potent phytochemical drugs.

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“…26 Nevertheless, few cases of hepatotoxicity have been reported, and its toxicity is not related to the dose or 4 Hepatitis is a common global health condition characterized by liver inflammation due to induced oxidative stress and membrane lipid peroxidation, which are the cornerstone mechanisms of this problem. 27 Hence, there is a need to avoid hepatitis by using natural products such as garlic, which effectively prevent many diseases, including hepatitis. 28,29 In the current study, we used an experimental model of female rats to handle easily and avoid age or sex variations.…”

Section: Discussionmentioning

confidence: 99%

Garlic Extract Alleviates Trastuzumab-Induced Hepatotoxicity in Rats Through Its Antioxidant, Anti-Inflammatory, and Antihyperlipidemic Effects

Mousa¹,

Soliman²,

Alhumaydhi³

et al. 2021

JIR

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Background: Trastuzumab is a new biological drug that has been used to treat breast and gastric cancer; however, its cardiotoxicity and hepatotoxicity limit its use. Garlic has antioxidant, anti-inflammatory, antihyperlipidemic, and anticancer effects. The present study aimed to evaluate the effects of garlic on trastuzumab-induced hepatotoxicity in a rat model. Methods: Twenty rats were divided into four equal groups as vehicle control (G1), garlic (G2), trastuzumab (G3), and trastuzumab+garlic (G4). All rats were sacrificed after eight weeks of treatment, followed by blood collection and excision of liver tissues for further analyses. The liver specimens were processed for histopathological (HP), immunohistochemical (expression of TNF-α and PCNA), immunofluorescent expression of Chk2 and p53, biochemical, and flow cytometry investigations to evaluate the extent of hepatocyte injury. The biochemical analysis was conducted for the activity of tissue antioxidants (GPX1, CAT, and SOD2), serum lipid profile, and liver enzymes, whereas ROS was performed by flow cytometry. Results:The results revealed remarkable structural changes in hepatocytes of G3 with significant increases in the numbers of inflammatory cells and positive PCNA cells, area % of collagen fibers, and immuno-expression of TNF-α, as well as a significant reduction in the nuclear expression of Chk2. In addition, significant reductions were noticed in the antioxidant enzymes (SOD2, CAT, and GPX1) activity of G3. In contrast, the levels of lipid profile tests (triglycerides, total cholesterol, LDLC, and HDLC), liver enzymes (ALT, AST, and ALP), and ROS revealed significant increases in rats of G3. Likewise, garlic administration in G4 restored all mentioned changes to their average levels deviated by trastuzumab. Conclusion: Based on the current results, garlic demonstrates hepatoprotective effects against trastuzumab-induced toxicity in rats. The study suggested for the first time that the coadministration of garlic with trastuzumab for treating breast or gastric cancer can augment their efficacy with minimal toxicity.

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Hepatoprotective effects of extracts, fractions and compounds from the stem bark of Pentaclethra macrophylla Benth: Evidence from in vitro and in vivo studies

Cited by 9 publications

References 25 publications

Silybin A fromSilybum marianumreprograms lipid metabolism to induce a cell fate-dependent class switch from triglycerides to phospholipids

Silybin A fromSilybum marianumreprograms lipid metabolism to induce a cell fate-dependent class switch from triglycerides to phospholipids

Recent insights into the hepatoprotective potential of medicinal plants and plant‐derived compounds

Garlic Extract Alleviates Trastuzumab-Induced Hepatotoxicity in Rats Through Its Antioxidant, Anti-Inflammatory, and Antihyperlipidemic Effects

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