Enhanced bioavailability and hepatoprotectivity of optimized ursolic acid–phospholipid complex

Biswas, Sayan; Mukherjee, Pulok K.; Harwansh, Ranjit K.; Bannerjee, Subhadip; Bhattacharjee, Pritorthi

doi:10.1080/03639045.2019.1583755

Cited by 32 publications

(16 citation statements)

References 49 publications

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“…UA is insoluble in water, with poor pharmacokinetic properties including poor oral bioavailability, low dissolution and weak membrane permeability [298]. Some new drug delivery technologies have been developed to overcome these problems including the uses of liposomes [280,[299][300][301][302], solid dispersions [303], niossomal gels [304], and nanoliposomes [278].…”

Section: Ursolic Acid (Ua)mentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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Numerous natural products originated from Chinese herbal medicine exhibit anti-cancer activities, including antiproliferative, pro-apoptotic, anti-metastatic, anti-angiogenic effects, as well as regulate autophagy, reverse multidrug resistance, balance immunity, and enhance chemotherapy in vitro and in vivo. To provide new insights into the critical path ahead, we systemically reviewed the most recent advances (reported since 2011) on the key compounds with anti-cancer effects derived from Chinese herbal medicine (curcumin, epigallocatechin gallate, berberine, artemisinin, ginsenoside Rg3, ursolic acid, silibinin, emodin, triptolide, cucurbitacin B, tanshinone I, oridonin, shikonin, gambogic acid, artesunate, wogonin, β-elemene, and cepharanthine) in scientific databases (PubMed, Web of Science, Medline, Scopus, and Clinical Trials). With a broader perspective, we focused on their recently discovered and/or investigated pharmacological effects, novel mechanism of action, relevant clinical studies, and their innovative applications in combined therapy and immunomodulation. In addition, the present review has extended to describe other promising compounds including dihydroartemisinin, ginsenoside Rh2, compound K, cucurbitacins D, E, I, tanshinone IIA and cryptotanshinone in view of their potentials in cancer therapy. Up to now, the evidence about the immunomodulatory effects and clinical trials of natural anti-cancer compounds from Chinese herbal medicine is very limited, and further research is needed to monitor their immunoregulatory effects and explore their mechanisms of action as modulators of immune checkpoints.

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Section: Ursolic Acid (Ua)mentioning

confidence: 99%

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

et al. 2019

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“…UA, a pentacyclic triterpenoid acid, is found abundantly in plants, especially in fruit and vegetable (Chang et al 2017). Although UA plays a variety of biological activities, its poor bioavailability seriously limits its clinical application (Biswas et al 2019). Structural modification of bioactive natural products has become an important means of developing potential bioactive molecules and leading drugs (Grabley and Sattler 2003).…”

Section: Discussionmentioning

confidence: 99%

“…UA plays an antitumor role in a variety of ways, including inhibition of proliferation, angiogenesis, invasion, metastasis, differentiation, and induction of tumour cell apoptosis (Zhang et al 2014). However, the poor bioavailability and efficacy of UA limit its clinical application in the treatment of lung cancer (Biswas et al 2019).…”

Section: Introductionmentioning

confidence: 99%

Ursolic acid derivative UA232 evokes apoptosis of lung cancer cells induced by endoplasmic reticulum stress

Gou

Luo

Wei

et al. 2020

Pharmaceutical Biology

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Context: Ursolic acid (UA), a natural product, shows a broad spectrum of anticancer effects. However, the poor bioavailability and efficacy of UA limit its clinical application. Objective: We developed novel analogues of UA with enhanced antitumor activities by the extensive chemical modification of UA. Materials and methods: We developed multiple compounds by structural modification of UA, and found that UA232 had stronger activity than UA. The effects of UA232 (0-50 lM) on inhibiting the proliferation of A549 and H460 cells were determined by CCK-8 for 24, 48, or 72 h. The proapoptotic effect of UA232 was analyzed by microscopy and flow cytometry, and the potential signal pathway affected by UA232 was further validated by Western blotting and flow cytometry. Results: Compared with UA, UA232 showed a stronger ability to inhibit the proliferation of lung cancer cells (IC 50 ¼ 5.4-6.1 lM for A549 and 3.9-5.7 lM for H460 cells). UA232 could induce not only cell cycle arrest in the G0/G1 phase but also apoptosis in both A549 and H460 cells. The treatment of UA232 could lead to an increase of CHOP expression rather than an increase in Bax or caspase-8, indicating that the apoptosis induced by UA232 was correlated with the endoplasmic reticulum stress (ER stress) pathway. Treatment with the ER stress-specific inhibitor, 4-PBA, decreased the ability of UA232 to induce apoptosis in A549 and H460 cells. Conclusion: UA232 induced apoptosis through the ER stress pathway, and showed stronger growthinhibitory effects in A549 and H460 cells compared to UA, which may be a potential anticancer drug to suppress the proliferation of lung cancer.

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“…In this regard, most researchers use organic solvents (e.g., acetone, ethanol, and dichloromethane) to dissolve ursolic acid or used organic solvents during preparation, which may be hazardous to humans. Further, its bioavailability has been assessed in the form of ursolic acid stearoyl glucoside [4], different phospholipid complexes [5], or nanoparticles [6]. When UA is combined with cyclodextrins, its solubility in water is greatly enhanced by the cyclic structure of the latter [7].…”

Section: Introductionmentioning

confidence: 99%

Different Forms of Ursolic Acid and Their Effect on Liver Regeneration

Žaloudková

Tichá

Nekvindová

et al. 2020

Evidence-Based Complementary and Alternative Medicine

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The aim of this study was to determine the effect of natural and encapsulated sources of ursolic acid on liver regeneration. Four ursolate sources were tested. Two forms of ursolic acid encapsulates were combined with cyclodextrins, i.e., gamma-CD (gCD) and beta-CD, and two natural sources were adjusted by homogenization (HAP) and micronization of apple peel using Jonagold apples. All ursolate forms were applied intragastrically in daily doses of 20 mg for 7 days. Laboratory rats were fed with standard laboratory diet. Further, gCD and MAP were also tested with a high-fat diet (6 weeks). Partial hepatectomy (PH) was performed 24 hours before the end of the experiment. The concentration of plasma hepatocyte growth factor (HGF) was determined with an immunoassay; simultaneously, the expression of HGF and CYP7A1 in the liver was quantified through qPCR. HGF expression and plasma levels were significantly increased 24 hours after PH in both the HAP (p=0.038) and HFgCD groups (p=0.036), respectively. The correlation between HGF expression and plasma values was significant (p=0.04). The positive effects on liver regeneration were found in both the gCD and HAP forms of ursolic acid, whose effects were confirmed through the upregulation of HGF.

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Enhanced bioavailability and hepatoprotectivity of optimized ursolic acid–phospholipid complex

Cited by 32 publications

References 49 publications

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Naturally occurring anti-cancer compounds: shining from Chinese herbal medicine

Ursolic acid derivative UA232 evokes apoptosis of lung cancer cells induced by endoplasmic reticulum stress

Different Forms of Ursolic Acid and Their Effect on Liver Regeneration

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