Obesity Scenarios: Ginkgo Biloba as a Potential Natural Remedy against Obesity and Its Molecular Mechanisms
Dramatic changes in dietary structure and nutrient intake over the last three decades have contributed to making obesity a global epidemic.
It is estimated that by 2025, >6% of men and 9% of women will be severely obese (BMI ≥ 35 kg/m2). Obesity has been identified as a key risk factor for a range of metabolic diseases, including stroke, diabetes, atherosclerosis, cardiovascular diseases, and certain types of cancer.
To counter obesity and related metabolic disorders, scientists have made significant efforts in developing safer and more effective pharmacotherapies for the prevention and treatment of obesity.
In recent decades, various herbal remedies have been identified with positive effects on weight loss or showing multiple beneficial effects in treating obesity-related disorders.
A growing body of evidence has demonstrated that some herbal medicines have safety profiles and clinical efficacy in preventing and treating obesity, with significant weight loss effects and few or no side effects.
However, unlike Western medications, herbal medicines are complex mixtures of a variety of chemically different natural constituents, which usually exert their therapeutic effects by interacting with various targets through different components in different ways. Therefore, efficiently identifying essential anti-obesity ingredients in herbal medicines and deciphering their mechanisms of action remain challenges for scientists in the field of ethnopharmacology.
Considering that most herbal constituents are poorly absorbed orally and a considerable portion of herbal constituents can be easily metabolized in vivo, it is more likely that most herbal constituents possess their anti-obesity effects by targeting multiple key gastrointestinal therapeutic targets.
It has been reported that several key digestive enzymes distributed in the human gastrointestinal system (such as gastric lipase and pancreatic lipase) play a crucial role in lipid absorption and have been confirmed as key therapeutic targets for preventing and treating obesity.
Particularly, human pancreatic lipase (hPL), a key serine hydrolase secreted by the human pancreas responsible for hydrolyzing about 70% of dietary lipids, has been validated as the most important target for regulating lipid absorption.
To efficiently identify naturally occurring hPL inhibitors in herbal medicines, a new strategy integrating the recently developed fluorescence-based hPL inhibition assay and global chemical analysis based on mass spectrometry has been proposed, enabling efficient identification of the most potent herbal medicine against hPL and deciphering its constituents.
After screening the anti-hPL effects of eighty herbal medicines, Ginkgo biloba extract was identified with the most potent anti-hPL activity. The global chemical profile of herbal constituents coupled with the hPL inhibition assay revealed that bioflavonoids and various flavonoids in Ginkgo biloba are key anti-hPL constituents.
Among all thirty-eight tested constituents, only sciadopitysin, bilobetin, quercetin, isoginkgetin, and ginkgetin showed potent anti-hPL effects (IC50 values <2.5 μM). Inhibition kinetic analyses suggested that sciadopitysin, bilobetin, quercetin, isoginkgetin, and ginkgetin acted as non-competitive hPL inhibitors, with Ki values <2 μM.
Docking simulations revealed that four bioflavonoids (sciadopitysin, bilobetin, isoginkgetin, and ginkgetin) could tightly bind to hPL in cavity 2, different from quercetin’s binding cavity on hPL.
Further investigations demonstrated that combinations of quercetin and a bioflavonoid-type hPL inhibitor (sciadopitysin or bilobetin) showed synergistic anti-hPL effects, suggesting that the multi-components in Ginkgo biloba extract may generate a more potent anti-hPL effect.
Overall, the study identified anti-obesity constituents in Ginkgo biloba and explored their anti-hPL mechanisms and synergistic effects at a molecular level, providing insights into understanding Ginkgo biloba’s anti-obesity mechanisms.
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