Subacute oral toxicology and toxicokinetics of pterostilbene, a novel Top1/Tdp1 inhibiting anti-tumor reagent

Sun, Chengfei; Liu, Ying; Zhang, Yutian; Huang, Haoyan; Chen, Huili; Chen, Jiaqin; Han, Luyao; Chen, Xiang; Chen, Xijing; Zhang, Yongjie

doi:10.1080/01480545.2022.2042014

Cited by 8 publications

(8 citation statements)

References 23 publications

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“…Consistent with our study, 200 mg PT/kg BW was safely used as an anticancer agent, as observed in the suppressed tumor growth in a hepatocellular carcinoma mouse model . In another study, doses of 200 and 500 mg PT/kg BW were orally administered to rats for 28 days without any significant toxicities . PT is proven to be a potential option in inflammatory OA therapy and prevention in this study.…”

Section: Discussionsupporting

confidence: 83%

“…52 In another study, doses of 200 and 500 mg PT/kg BW were orally administered to rats for 28 days without any significant toxicities. 53 PT is proven to be a potential option in inflammatory OA therapy and prevention in this study. The narrow space of the joint and loss of chondrocytes in OCP-induced OA were recovered into a wider joint space and relatively complete chondrocytes after PT treatment (Figure 1E).…”

Section: ■ Discussionmentioning

confidence: 82%

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Pterostilbene Protects against Osteoarthritis through NLRP3 Inflammasome Inactivation and Improves Gut Microbiota as Evidenced by In Vivo and In Vitro Studies

Lee,

Chang,

Cheng

et al. 2024

J. Agric. Food Chem.

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Osteoarthritis (OA) is a persistent inflammatory disease, and long-term clinical treatment often leads to side effects. In this study, we evaluated pterostilbene (PT), a natural anti-inflammatory substance, for its protective effects and safety during prolonged use on OA. Results showed that PT alleviated the loss of chondrocytes and widened the narrow joint space in an octacalcium phosphate (OCP)-induced OA mouse model (n = 3). In vitro experiments demonstrate that PT reduced NLRP3 inflammation activation (relative protein expression: C: 1 ± 0.09, lipopolysaccharide (LPS): 1.14 ± 0.07, PT: 0.91 ± 0.07, LPS + PT: 0.68 ± 0.04) and the release of inflammatory cytokines through NF-κB signaling inactivation (relative protein expression: C: 1 ± 0.03, LPS: 3.49 ± 0.02, PT: 0.66 ± 0.08, LPS + PT: 2.78 ± 0.05), ultimately preventing cartilage catabolism. Interestingly, PT also altered gut microbiota by reducing inflammation-associated flora and increasing the abundance of healthy bacteria in OA groups. Collectively, these results suggest that the PT can be considered as a protective strategy for OA.

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Section: Discussionsupporting

confidence: 83%

Section: ■ Discussionmentioning

confidence: 82%

Pterostilbene Protects against Osteoarthritis through NLRP3 Inflammasome Inactivation and Improves Gut Microbiota as Evidenced by In Vivo and In Vitro Studies

Lee,

Chang,

Cheng

et al. 2024

J. Agric. Food Chem.

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“…16 In another recent study, intragastric administration of pterostilbene up to 500 mg/kg indicated no special concerns for toxicity. 28 Previously, Riche et al reported the efficacy and safety of chemically synthesized pterostilbene at 125 mg twice daily for 52 days in 80 hypercholesteremic patients [16]. A short-term safety of P. marsupium extract containing pterostilbene was established for 450 mg once daily or 225 mg twice daily dose in five subjects in each arm for 14 days.…”

Section: Discussionmentioning

confidence: 99%

A Short-Term Safety Evaluation of Silbinol^®- an Extract from Pterocarpus marsupium in Healthy Adults- a Randomized, Double-Blind, Placebo-Controlled Study

Majeed,

Nagabhushanam,

Paulose

et al. 2023

J Evid Based Complementary Altern Med

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Background: Pterostilbene is an active molecule from the bark of the Pterocarpus marsupium tree with antioxidant and anti-inflammatory properties. Objective: This study aimed to evaluate the clinical safety of a standardized P. marsupium extract (PME) containing 90% pterostilbene (200 mg per day) in healthy adults. Methods: In a randomized, double-blind, placebo-controlled study, 60 healthy adult participants (27 males and 33 females) were randomized to receive PME-100 mg or placebo capsule twice a day for two months. The primary objectives of the study were to assess any changes in laboratory parameters, vital signs, and the occurrence of adverse events from screening to the final visit. Serum antioxidant enzyme levels were evaluated as a secondary outcome. Results: The hematological, lipid, glycemic, thyroid profiles and liver and renal functions remained within the normal range in all participants, with no difference between PME and placebo. Vital signs, including blood pressure, pulse rate, body weight, body mass index and electrocardiogram, did not reveal any significant differences between the PME and placebo groups at the beginning and end of the study. No serious adverse events were observed in any participant throughout the study period. The serum antioxidant profile was not significantly different between the treatment groups, although the glutathione levels were relatively higher in the PME group. Conclusions: Scientific evaluation of clinical safety of standardized extract is mandatory for its use as a supplement for various health benefits. The results of this study convincingly establish the safety of PME (>90% Pterostilbene) at 200 mg/day (100 mg bid) for human use. The study was approved by the Institutional Ethics Committee of BGS Global Institute of Medical Sciences & Hospital, Bangalore with the registration number CTRI/2019/08/020736.

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“…12 In addition, PTE was recognized as a safe and tolerable compound in both animals and humans. 13,14 Thus, it is believed that PTE is a health-promoting nutraceutical with guaranteed efficacy and safety profile.…”

Section: ■ Introductionmentioning

confidence: 99%

“…More recently, it is reported that PTE exhibited potent antitumor activities against various types of cancers. , PTE was shown to inhibit tumor cell growth by inducing autophagy and apoptosis, altering cell cycle, and inhibiting tumor cell migration and invasion . In addition, PTE was recognized as a safe and tolerable compound in both animals and humans. , Thus, it is believed that PTE is a health-promoting nutraceutical with guaranteed efficacy and safety profile.…”

Section: Introductionmentioning

confidence: 99%

Phase I Metabolism of Pterostilbene, a Dietary Resveratrol Derivative: Metabolite Identification, Species Differences, Isozyme Contribution, and Further Bioactivation

Liu

Sun

Zhang

et al. 2022

J. Agric. Food Chem.

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Pterostilbene (PTE), a dietary derivative of resveratrol, displayed pleiotropic health-promoting activities. This study aimed to explore the metabolic profiles and species differences of the phase I metabolism of PTE and to investigate subsequent detoxification after PTE bioactivation. PTE was found to be biotransformed to two pharmacologically active metabolites, pinostilbene and 3′-hydroxypterostilbene, in vivo and in vitro with substantial species differences. Human CYP1A2 was proved to be mainly responsible for the demethylation and 3′-hydroxylation of PTE, with its contribution to a demethylation of 94.5% and to a 3′-hydroxylation of 97.9%. An in vitro glutathione trapping experiment revealed the presence of an ortho-quinone intermediate formed by further oxidation of 3′-hydroxypterostilbene. Human glutathione S-transferase isoforms A2, T1, and A1 inactivated the ortho-quinone intermediate by catalyzing glutathione conjugation, implicating a potential protective pathway against PTE bioactivation-derived toxicity. Overall, this study provided a comprehensive view of PTE phase I metabolism and facilitated its further development as a promising nutraceutical.

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Subacute oral toxicology and toxicokinetics of pterostilbene, a novel Top1/Tdp1 inhibiting anti-tumor reagent

Cited by 8 publications

References 23 publications

Pterostilbene Protects against Osteoarthritis through NLRP3 Inflammasome Inactivation and Improves Gut Microbiota as Evidenced by In Vivo and In Vitro Studies

Pterostilbene Protects against Osteoarthritis through NLRP3 Inflammasome Inactivation and Improves Gut Microbiota as Evidenced by In Vivo and In Vitro Studies

A Short-Term Safety Evaluation of Silbinol^®- an Extract from Pterocarpus marsupium in Healthy Adults- a Randomized, Double-Blind, Placebo-Controlled Study

Phase I Metabolism of Pterostilbene, a Dietary Resveratrol Derivative: Metabolite Identification, Species Differences, Isozyme Contribution, and Further Bioactivation

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Subacute oral toxicology and toxicokinetics of pterostilbene, a novel Top1/Tdp1 inhibiting anti-tumor reagent

Cited by 8 publications

References 23 publications

Pterostilbene Protects against Osteoarthritis through NLRP3 Inflammasome Inactivation and Improves Gut Microbiota as Evidenced by In Vivo and In Vitro Studies

Pterostilbene Protects against Osteoarthritis through NLRP3 Inflammasome Inactivation and Improves Gut Microbiota as Evidenced by In Vivo and In Vitro Studies

A Short-Term Safety Evaluation of Silbinol®- an Extract from Pterocarpus marsupium in Healthy Adults- a Randomized, Double-Blind, Placebo-Controlled Study

Phase I Metabolism of Pterostilbene, a Dietary Resveratrol Derivative: Metabolite Identification, Species Differences, Isozyme Contribution, and Further Bioactivation

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A Short-Term Safety Evaluation of Silbinol^®- an Extract from Pterocarpus marsupium in Healthy Adults- a Randomized, Double-Blind, Placebo-Controlled Study