Effects of Ganoderma lucidum polysaccharides against doxorubicin-induced cardiotoxicity

Xu, Fan; Li, Xiao; Xiao, Xu; Liu, Lan-fang; Zhang, Li; Lin, Pingping; Zhang, Shenglin; Liu, Qingshan

doi:10.1016/j.biopha.2017.08.118

Cited by 42 publications

(27 citation statements)

References 39 publications

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“…IL-6 was shown to activate the apoptosis-associated factors Caspase3 and Smad3, and decrease expression of the anti-apoptotic factor Bcl2, resulting in the apoptosis of cardiomyocytes cultured under hypoxic conditions [44]. It was reported that a reduction of p-P65 expression attenuated the apoptosis of H9c2 rat cardiomyocytes, while TNF-α caused a significant increase in the expression of apoptotic proteins Bax, and Caspase 3, which directly correlated with subsequent apoptosis [45,46]. Consistent with these findings, our data showed that PGE1 significantly diminished apoptosis, and decreased the expression of IL-2, IL-6, P-p65, and TNF-α.…”

Section: Discussionmentioning

confidence: 99%

Prostaglandin E1 protects cardiomyocytes against hypoxia-reperfusion induced injury via the miR-21-5p/FASLG axis

et al. 2019

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Background: Prostaglandin-E1 (PGE1) is a potent vasodilator with anti-inflammatory and antiplatelet effects. However, the mechanism by which PGE1 contributes to the amelioration of cardiac injury remains unclear. Methods: The present study was designed to investigate how PGE1 protects against hypoxia/reoxygenation (H/R)-induced injuries by regulating microRNA-21-5p (miR-21-5p) and fas ligand (FASLG). Rat H9C2 cells and isolated primary cardiomyocytes were cultured under hypoxic conditions for 6 h (6H, hypoxia for 6 h), and reoxygenated for periods of 6 (6R, reoxygenation for 6 h), 12, and 24 h, respectively. Cells from the 6H/6R group were treated with various doses of PGE1; after which, their levels of viability and apoptosis were detected. Results: The 6H/6R treatment regimen induced the maximum level of H9C2 cell apoptosis, which was accompanied by the highest levels of Bcl-2-associated X protein (Bax) and cleaved-caspase-3 expression and the lowest level of B-cell lymphoma 2 (Bcl-2) expression. Treatment with PGE1 significantly diminished the cell cytotoxicity and apoptosis induced by the 6H/6R regimen, and also decreased expression of IL-2, IL-6, P-p65, TNF-α, and cleaved-caspase-3. In addition, we proved that PGE1 up-regulated miR-21-5p expression in rat cardiomyocytes exposed to conditions that produce H/R injury. FASLG was a direct target of miR-21-5p, and PGE1 reduced the ability of H/R-injured rat cardiomyocytes to undergo apoptosis by affecting the miR-21-5p/FASLG axis. In addition, we proved that PGE1 could protect primary cardiomyocytes against H/R-induced injuries. Conclusions: These results indicate that PGE1 exerts cardioprotective effects in H9C2 cells during H/R by regulating the miR-21-5p/FASLG axis.

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Section: Discussionmentioning

confidence: 99%

Prostaglandin E1 protects cardiomyocytes against hypoxia-reperfusion induced injury via the miR-21-5p/FASLG axis

et al. 2019

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“…The Lingzhi and cytotoxic drug combinations were also found to relieve some adverse effects in animal studies; for example, they reduced damage to different organs, including the intestine [162,173], the kidney [64][65][66][174][175][176][177][178][179][180], the liver [66,86,157,164,165], and the heart [157,181,182]; and their adverse effects, such as nausea and vomiting [147,183,184], mutation [185], and neural tube defects [186].…”

Section: B Preclinical and Mechanistic Evidencementioning

confidence: 99%

“…Some studies have evaluated the mechanism underlying the protective effects of the mushroom-drug combinations against chemotherapy-induced side effects. For example, the mechanism underlying the reduction of doxorubicin-induced myocardial damage was found to be via the modulation of cardiac enzymes and reduction of the oxidative stress (such as increase in glutathione S-transferase (GST) and glutathione peroxidase (GPx) levels) in myocardial cells by Lingzhi or Ganoderma polysaccharides [181,182]. Similarly, Lingzhi and its polysaccharides likely increased renocortical antioxidant levels and relieved the oxidative stress, thereby ameliorating cisplatin-induced renal damage.…”

Section: B Preclinical and Mechanistic Evidencementioning

confidence: 99%

“…Other effects in pre-clinical studies Several chemotherapy drugs are known to cause oxidative stress which damage tumor cells but concomitantly damage normal cells and produce adverse effects [189]. The co-administration of Lingzhi with cytotoxic drugs, including cisplatin, cyclophosphamide, doxorubicin, and methotrexate increased the total antioxidant capacity and levels of different antioxidant enzymes, including superoxide dismutase (SOD), glutathione, GPx, and catalase, and decreased malondialdehyde levels, thereby reducing the oxidative stress [64,81,150,157,162,[175][176][177][178][179][180][181][182][190][191][192]. In an in-vitro study, the co-administration of Yunzhi with cisplatin prevented the decrease in SOD activity by mimicking it to protect normal healthy cells while selectively promoting the decrease in SOD activity and increase in lipid peroxide levels in cancer cells, both of which synergistically increased tumor inhibition while leaving normal cells unaffected [131].…”

Section: B Preclinical and Mechanistic Evidencementioning

confidence: 99%

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Herb–drug interactions between the medicinal mushrooms Lingzhi and Yunzhi and cytotoxic anticancer drugs: a systematic review

et al. 2020

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Background: Lingzhi and Yunzhi are medicinal mushrooms commonly used with cytotoxic chemotherapy in cancer patients in Asian countries. The current systematic review aims to identify potential pharmacokinetic or pharmacodynamic interactions from the existing literature to ensure their effective and safe combination usage in cancer patients. Methods: A systematic search was conducted on nine major Chinese and English databases, including China Journal Net, Allied and Complementary Medicine Database, and Ovid MEDLINE ® , etc., to identify clinical, animal, and in-vitro studies that evaluate the effect of combined use of Lingzhi or Yunzhi with cytotoxic drugs. The Jadad scale was used to assess the quality of clinical studies. Results: This search identified 213 studies, including 77 clinical studies that reported on the combined use of cytotoxic drugs with Yunzhi (n = 56) or Lingzhi (n = 21). Majority of these clinical studies demonstrated modest methodological quality. In clinical practice, the most commonly used cytotoxic drugs with Lingzhi were cisplatin, 5-fluorouracil (5-FU) and paclitaxel, whereas Tegafur/uracil (UFT)/Tegafur, 5-FU, and mitomycin were the ones used more often with Yunzhi. Only two clinical pharmacokinetic studies were available showing no significant interactions between Polysaccharide K (PSK) and Tegafur. From the pharmacodynamic interactions perspective, combination uses of Yunzhi/Lingzhi with cytotoxic drugs in clinical practice could lead to improvement in survival (n = 31) and quality of life (n = 17), reduction in tumor lesions (n = 22), immune modulation (n = 38), and alleviation of chemotherapy-related side effects (n = 14) with no reported adverse effects. Conclusion: Our findings suggest that the clinical combination use of Lingzhi or Yunzhi with cytotoxic drugs could enhance the efficacy and ameliorate the adverse effects of cytotoxic drugs, leading to improved quality of life in cancer patients. More high quality clinical studies including pharmacokinetic herb-drug interactions studies are warranted to verify these observations and mechanisms involved. Based on the high quality clinical data, pharmacoepidemiology methods and bioinformatics or data mining could be adopt for further identification of clinical meaningful herb-drug interactions in cancer therapies.

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“…It is known to synthesize phytochemicals such as polysaccharides, adenosine, ergosterols, ganoderic acids, coumarin, lactones, mannitol, organic germanium, triterpenoids, and rare minerals (Boh, Berovic, Zhang, & Lin, ). These phytoconstituents helps in improving blood circulation, eliminates fatigue, enhances energy, strengthens immune system, and helps in detoxification and controlling heart disease, atherosclerosis, liver disease, diabetess and general infection (Liu et al, , ; Min, Nakamura, Miyashiro, Bae, & Hattori, ; Sliva, ; Wihastuti & Heriansyah, ; Wu, Ho, Nan, & Chen, ; Xu et al, ; Zhao et al, ).…”

Section: Introductionmentioning

confidence: 99%

Pharmacological effects ofGanoderma lucidumextract against high‐altitude stressors and its subchronic toxicity assessment

Sharma

Tulsawani

Agrawal³

2019

J Food Biochem

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Acclimatization is a major pathophysiological concern during ascent to high altitude and may cause mortality in unacclimatized individuals. Absence of target drugs, especially prophylactics, emphasizes the need for development of herbal agents. Present study revealed that animals pre‐administered with aqueous extract of Ganoderma lucidum (GLAQ) dose dependently (50, 100, 200 mg/kg) delayed onset of convulsion following severe hypoxia (SH) and restored rectal temperature post‐cold restraint (CR) and hypobaric hypoxia (HBH). The compromised antioxidant status (MDA, GSH, SOD, GPx), biochemical (ALT, AST, glucose, triglycerides, cholesterol, urea), and hematological parameters (red blood cells, white blood cells) were ameliorated with GLAQ treatment. Further, extract modulated inflammatory and thermogenic response by attenuating pro‐inflammatory cytokines (NFĸB, TNFα, IL6) and restoring UCP1, SIRT1, respectively. Notably, extract did not produce any noxious effects subchronically in rats of both sexes with GLAQ administered at 100, 500, and 1,000 mg/kg in a single dose/day for 90 days, deeming it fit for therapeutic purpose. Practical applications GLAQ exhibited better efficacy compared to internal control (gallic acid) suggest that array of bioactive compounds in extract might contribute toward efficacy. Further, antistress properties of GLAQ against multiple stressors including SH, CR, and HBH demonstrate its therapeutic potential for inducing rapid acclimatization and preventing mountain sickness. Conclusively, the present study based on Ganoderma lucidum extract intents to fill the lacunae behind development of nontoxic therapeutic agent for controlling high altitude‐related maladies.

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Effects of Ganoderma lucidum polysaccharides against doxorubicin-induced cardiotoxicity

Cited by 42 publications

References 39 publications

Prostaglandin E1 protects cardiomyocytes against hypoxia-reperfusion induced injury via the miR-21-5p/FASLG axis

Prostaglandin E1 protects cardiomyocytes against hypoxia-reperfusion induced injury via the miR-21-5p/FASLG axis

Herb–drug interactions between the medicinal mushrooms Lingzhi and Yunzhi and cytotoxic anticancer drugs: a systematic review

Pharmacological effects ofGanoderma lucidumextract against high‐altitude stressors and its subchronic toxicity assessment

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