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(A) Levels of malondialdehyde (MDA) measured in retroperitoneal adipose tissue of the HFD and HFD+GbE groups (µM/mg protein); (B) retroperitoneal adipocyte volume of the HFD and HFD+GbE groups (ρL). Values are expressed as the mean ± SEM (n = 5–7).
Source publication
The rapid increase in the number of individuals with obesity, over the past four decades, is triggered by a number of complex interactions among factors. Despite the plethora of treatments available, side effects are commonly observed and, in this context, herbal medicines have been employed as an alternative form of therapy. Ginkgo biloba extract...
Citations
... The use of Ginkgo to improve symptoms in patients with oxidative inflammation-related diseases is thought to be associated with improved tissue perfusion and hypoxia tolerance. Ginkgo's flavonoid glycosides exhibit antioxidant and anti-inflammatory properties, which can help reduce endothelial cell damage caused by free radical oxidation [28,[55][56][57][58]. Figure 3 shows the major bioactive components found in this plant, parts of the GB tree, and the chemical compounds classified by class, and Table 1 lists the chemical structure of bioactive compounds, parts of the GB tree, and their effects. Furthermore, GB extracts are shown to induce biphasic dose responses in different cell types and endpoints. ...
... GbE upregulates the expression of lactoylglutathione lyase (glyoxalase I), an enzyme that has anti-inflammatory properties. This enzyme is responsible for neutralizing methylglyoxal, a highly toxic compound produced during glycolysis and lipid peroxidation that can trigger inflammation [58,113]. ...
Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords-GB in AD and dementia-yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761 ® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show that Ginkgo biloba has promising potential for the treatment of these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.
... The use of Ginkgo to improve symptoms in patients with oxidative inflammation-related diseases is thought to be associated with improved tissue perfusion and hypoxia tolerance. Ginkgo's flavonoid glycosides exhibit antioxidant and antiinflammatory properties, which can help reduce endothelial cell damage caused by free radical oxidation [28,[55][56][57][58]. Figure 4 shows the major bioactive components found in this plant, parts of the GB tree, and the chemical compounds classified by class and and Table 1 lists the chemical structure of bioactive compounds, parts of the GB tree, and their effects. 20 Tissue damage activates an inflammatory cascade, a natural response that includes complex molecular reactions and cellular responses. ...
... GbE upregulates the expression of lactoylglutathione lyase (glyoxalase I), an enzyme that has anti-inflammatory properties. This enzyme is responsible for neutralizing methylglyoxal, a highly toxic compound produced during glycolysis and lipid peroxidation that can trigger inflammation [58,110]. ...
Alzheimer's disease (AD) is a stealthy and progressive neurological disorder that is a leading cause of dementia in the global elderly population, imposing a significant burden on both the elderly and society. Currently, the condition is treated with medications that alleviate symptoms. Nonetheless, these drugs may not consistently produce the desired results and can cause serious side effects. Hence, there is a vigorous pursuit of alternative options to enhance the quality of life for patients. Ginkgo biloba (GB), an herb with historical use in traditional medicine, contains bioactive compounds such as terpenoids (Ginkgolides A, B, and C), polyphenols, organic acids, and flavonoids (quercetin, kaempferol, and isorhamnetin). These compounds are associated with anti-inflammatory, antioxidant, and neuroprotective properties, making them valuable for cognitive health. A systematic search across three databases using specific keywords GB in AD and dementia yielded 1702 documents, leading to the selection of 15 clinical trials for synthesis. In eleven studies, GB extract/EGb 761® was shown to improve cognitive function, neuropsychiatric symptoms, and functional abilities in both dementia types. In four studies, however, there were no significant differences between the GB-treated and placebo groups. Significant improvements were observed in scores obtained from the Mini-Mental State Examination (MMSE), Short Cognitive Performance Test (SKT), and Neuropsychiatric Inventory (NPI). While the majority of synthesized clinical trials show Ginkgo biloba has promising potential in these conditions, more research is needed to determine optimal dosages, effective delivery methods, and appropriate pharmaceutical formulations. Furthermore, a thorough assessment of adverse effects, exploration of long-term use implications, and investigation into potential drug interactions are critical aspects that must be carefully evaluated in future studies.
... Decorin may participate in immune response and induce inflammatory processes, but it is also associated with AT homeostasis and metabolic response. Recently, Hirata et al. studied proteome and oxidative stress protection potential in diet-induced obese rats treated with Ginko biloba extract and found that upregulation of decorin was accompanied by downregulation of oxidative stress-related protein [133]. It has recently been observed that decorin is responsible for maintaining glucose tolerance (Figure 1) [130]. ...
Obesity is a characteristic disease of the twenty-first century that is affecting an increasing percentage of society. Obesity expresses itself in different phenotypes: normal-weight obesity (NWO), metabolically obese normal-weight (MONW), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO). A range of pathophysiological mechanisms underlie the occurrence of obesity, including inflammation, oxidative stress, adipokine secretion, and other processes related to the pathophysiology of adipose tissue (AT). Body mass index (BMI) is the key indicator in the diagnosis of obesity; however, in the case of the NWO and MONW phenotypes, the metabolic disturbances are present despite BMI being within the normal range. On the other hand, MHO subjects with elevated BMI values do not present metabolic abnormalities. The MUO phenotype involves both a high BMI value and an abnormal metabolic profile. In this regard, attention has been focused on the variety of molecules produced by AT and their role in the development of obesity. Nesfatin-1, neuregulin 4, myonectin, irisin, and brain-derived neurotrophic factor (BDNF) all seem to have protective effects against obesity. The primary mechanism underlying the action of nesfatin-1 involves an increase in insulin sensitivity and reduced food intake. Neuregulin 4 sup-presses lipogenesis, decreases lipid accumulation, and reduces chronic low-grade inflammation. Myonectin lowers the amount of fatty acids in the bloodstream by increasing their absorption in the liver and AT. Irisin stimulates the browning of white adipose tissue (WAT) and consequently in-creases energy expenditure, additionally regulating glucose metabolism. Another molecule, BDNF, has anorexigenic effects. Decorin protects against the development of hyperglycemia, but may also contribute to proinflammatory processes. Similar effects are shown in the case of visfatin and chemerin, which may predispose to obesity. Visfatin increases adipogenesis, causes cholesterol accumulation in macrophages, and contributes to the development of glucose intolerance. Chemerin induces angiogenesis, which promotes the expansion of AT. This review aims to discuss the role of adipokines and myokines in the pathogenesis of the different obesity phenotypes.
... Flavonoids and terpenoids are suggested to be the pharmacologically active components of GBE [22,23]. Considerable evidence has shown that GBE is effective in the prevention and alleviation of atherosclerosis [24], cardiovascular diseases [25,26], obesity [27,28], MAFLD [29], neurological diseases [30], among others. Although the beneficial role of GBE can be partially attributed to its antioxidant activity, recent findings strongly suggested that GBE and its components can interact with gut microbiota to perform biological functions. ...
... As a natural antioxidant, GBE has been reported to be beneficial to health by helping the body resist harmful oxidative stress and reducing the infiltration of inflammatory cells and inflammatory cytokines [20,49]. Currently, GBE is widely used in the alleviation of metabolic diseases such as obesity and MAFLD due to its excellent lipid-lowering effect [27][28][29], while the pharmacological mechanism of GBE on anti-FLHS remains unelucidated. ...
Background
Ginkgo biloba extract (GBE) is evidenced to be effective in the prevention and alleviation of metabolic disorders, including obesity, diabetes and fatty liver disease. However, the role of GBE in alleviating fatty liver hemorrhagic syndrome (FLHS) in laying hens and the underlying mechanisms remain to be elucidated. Here, we investigated the effects of GBE on relieving FLHS with an emphasis on the modulatory role of GBE in chicken gut microbiota.
Results
The results showed that GBE treatment ameliorated biochemical blood indicators in high-fat diet (HFD)-induced FLHS laying hen model by decreasing the levels of TG, TC, ALT and ALP. The lipid accumulation and pathological score of liver were also relieved after GBE treatment. Moreover, GBE treatment enhanced the antioxidant activity of liver and serum by increasing GSH, SOD, T-AOC, GSH-PX and reducing MDA, and downregulated the expression of genes related to lipid synthesis ( FAS , LXRα , GPAT1 , PPARγ and ChREBP1 ) and inflammatory cytokines ( TNF-α, IL-6, TLR4 and NF-κB ) in the liver. Microbial profiling analysis revealed that GBE treatment reshaped the HFD-perturbed gut microbiota, particularly elevated the abundance of Megasphaera in the cecum. Meanwhile, targeted metabolomic analysis of SCFAs revealed that GBE treatment significantly promoted the production of total SCFAs, acetate and propionate, which were positively correlated with the GBE-enriched gut microbiota. Finally, we confirmed that the GBE-altered gut microbiota was sufficient to alleviate FLHS by fecal microbiota transplantation (FMT).
Conclusions
We provided evidence that GBE alleviated FLHS in HFD-induced laying hens through reshaping the composition of gut microbiota. Our findings shed light on mechanism underlying the anti-FLHS efficacy of GBE and lay foundations for future use of GBE as additive to prevent and control FLHS in laying hen industry.
... Standardised Ginkgo biloba extract (GbE) has been identified as a GM modulator, as observed in studies evaluating atherosclerosis and depression (Chen et al., 2019;Lv et al., 2021). The standardised GbE composition, with 24% flavonoids and 6% terpenoids, has shown antioxidant, anti-inflammatory and anti-obesogenic properties (Hirata et al., 2015;2019a;2019b). Combined, the properties attributed to GbE may offer a potential therapeutic approach to address obesity and related disorders. ...
... In the present study, HFD+G showed reduced food intake in comparison to HFD (Fig. 1). This result has been previously reported by our group Hirata et al., 2015;2019a;2019b). In order to confirm that the modulatory changes induced by GbE found in the present study were not a secondary effect attributed to reduced energy intake, a pair-fed group was also assessed, in which its calorie intake was matched to the GbE-receiving group, but under saline supplementation. ...
... In addition, although we did not find changes in body weight gain after GbE supplementation, our study involved a 2-week supplementation protocol, which is probably too brief to cause an effect, as well as a relatively small sample size. Previous GbE studies featuring larger sample sizes have identified a significant effect on body weight gain (Hirata et al., 2015;2019a;2019b). ...
Background: Gut microbiota (GM) modulation has been considered a nutritional approach to manage obesity. Reduced Firmicutes/Bacteroidetes ratio (F/B) is associated with reduced energy harvesting capacity from the diet, ameliorates endotoxemia and inflammation, and restores gut hormone signaling related to hypothalamic control of energy homeostasis. As anti-obesogenic and anti-inflammatory properties have been attributed to Ginkgo biloba extract (GbE), the present study investigated whether GbE supplementation for two weeks modulates the GM composition of obese rats. Method: Fifty-six 2-month-old male Wistar rats were submitted to a lard-rich diet-induced obesity protocol for 60 days (high-fat diet, HFD). Following the obesity-inducing period, rats were gavaged daily with GbE at 500 mg/kg (HFD+G group), or saline (HFD group), for 14 days. A 3rd group (pair-fed group, PF) was performed by mimicking the HFD group (saline administration) but with its food intake matched to the HFD+G group. Rats were euthanized on the 14th supplementation day. Stool DNA was extracted and amplified with V3–V4 region primers of the 16S rRNA gene. Results: In comparison to both HFD and PF groups, GbE supplementation increased the number of Bacteroidetes colon community and concomitantly reduced the abundance of Firmicutes, reducing the F/B ratio. Hierarchical clustering showed that communities of the HFD+G group were less likely related to HFD and PF groups. Conclusion: As GbE modulated the GM structure and diversity in GbE-supplemented obese rats, our results show that GbE possesses phytotherapeutic potential to modulate obesity by improving GM and lessening the consequences of obesity-related GM dysbiosis.
... In fact, promoting adipocyte differentiation has been considered a strategy for the healthy expansion of adipose tissue, preventing the development of diseases caused by hypertrophic obesity, including type-2 diabetes, cardiovascular disease, and cancer [21,22]. Considering the previously observed GbE effect on white adipose tissue remodeling [15][16][17], we hypothesized whether GbE would be able to stimulate adipogenesis. This hypothesis has indeed been confirmed in the present study since the GbE treatment anticipated the gene expression involved in adipogenesis in addition to promoting morphological changes in the 3T3-L1 treated preadipocytes. ...
... Previous studies from our group have demonstrated a remodeling potential of the GbE treatment in white adipose tissue of diet-induced obese rats. The supplementation with GbE (500 mg/kg) for 14 days reduced both the retroperitoneal [16] and epididymal adipocyte volume to the equivalent of lean rats, in addition to reduced epididymal acetate accumulation and [1-14C]-acetate incorporation into fatty acids, when compared to nontreated obese rats [17]. In light of this evidence, our findings reinforce the GbE adipogenic potential, which could be an interesting therapeutic target in the context of a supplementary treatment for hypertrophic obesity. ...
Smaller adipocytes are related to the reversal of metabolic disorders, suggesting that molecules that can act in the adipogenesis pathway are of great interest. The objective of this study was to investigate the effect of Ginkgo biloba extract (GbE) in modulating the differentiation in preadipocytes. 3T3-L1 preadipocytes were differentiated for 7 days into adipocytes without (control group) and with GbE at 1.0 mg/mL. Lipid content and gene expression were analyzed on day 7 (D7) by Oil Red O staining and PCR Array Gene Expression. Western blotting analysis of the key adipogenesis markers was evaluated during the differentiation process at days 3 (D3), 5 (D5), and 7 (D7). GbE increased lipid content and raised the gene expression of the main adipogenesis markers. Key proteins of the differentiation process were modulated by GbE, since C/EBPβ levels were decreased, while C/EBPα levels were increased at D7. Regarding the mature adipocytes’ markers, GbE enhanced the levels of both FABP4 at D5, and perilipin at D3 and D5. In summary, the present findings showed that GbE modulated the adipogenesis pathway suggesting that the treatment could accelerate the preadipocyte maturation, stimulating the expression of mature adipocyte proteins earlier than expected.
... It was also found that the extract has more prophylactic antioxidant activity than vitamin E [44][45][46][47]. Hirata et al. [48] concluded that G. biloba extract (GbE) acts as an antioxidant agent. Furthermore, it improved the proteome profile and oxidative stress response in adipose tissue of diet-induced obese rats. ...
Background
Ginkgo (Ginkgo biloba) is a living fossil and a deciduous tree, which has extracts with antidiabetic, antioxidant anticancer, antihypertensive, immunestimulative, hepato-protective and antimicrobial activities, memory enhancement efficiency and beneficial effects against neurodegenerative disease.
Objective
The goal of this manuscript is survey on medicinal values and natural benefits of Ginkgo.
Methods
This review evaluated publication in MEDLINE/PubMEd database and Google Scholar. The keywords used to electronically search were Ginkgo biloba, living fossil, bioactive components and traditional Chinese medicine.
Results
Its main active constituents extracts are flavones glycosides such kaempferol, quercetin and isorhamnetin, terpene lactones, alkyphenols, proanthocyanadins, rhamnose, glucose, D-glucaric acid, ginkgolic acid, organic acids such as hydroxykinurenic, kynurenic, protocatechic, shikimic and vanillic. Ginkgo kernels have been used as medicine or eaten as nut in traditional medicinal science. The most notable pharmaceutical application of Ginkgo are in cardiovascular disease, Alzheimer, impaired cerebral performance, vascular insufficiency, antidepressant-induced sexual dysfunction, premenstrual syndrome, liver fibrosis, vascular disease, tinnitus, macular degeneration, memory and vertigo.
Conclusion
Development of modern drugs from Ginkgo by considering the importance of traditional medicinal Asian science with further researches should be emphasized.
... Indeed, we have previously reported that GbE supplementation for 14 days reduced food intake, body mass gain, and visceral adiposity in diet-induced obese male rats (DIO) [15][16][17]. Moreover, GbE improved insulin signaling in both the retroperitoneal adipose tissue and gastrocnemius muscle [15,16], as well as modulated proteins involved in lipid metabolism [17,18], and attenuated the inflammation and oxidative stress of retroperitoneal fat depot in obese rats [17,18]. ...
... Indeed, we have previously reported that GbE supplementation for 14 days reduced food intake, body mass gain, and visceral adiposity in diet-induced obese male rats (DIO) [15][16][17]. Moreover, GbE improved insulin signaling in both the retroperitoneal adipose tissue and gastrocnemius muscle [15,16], as well as modulated proteins involved in lipid metabolism [17,18], and attenuated the inflammation and oxidative stress of retroperitoneal fat depot in obese rats [17,18]. ...
... Since no alterations were observed in the protein levels of POMC, 5-HT1B, and 5-HT2C, neither in food intake nor in body mass, we hypothesize that the GbE hypophagic activity might occur after a prolonged GbE supplementation. Indeed, this hypothesis is aligned with previous studies from our group in which the GbE 14-day supplementation reduced food intake, body weight gain, and visceral adiposity in DIO rats [15,16,18]. We have also reported that GbE modulated hypothalamic and hippocampal anorexigenic mechanisms after a 14-day treatment protocol, supporting a hypothesis for a time- ...
Previous studies have shown that Ginkgo biloba extract (GbE) reduces food intake and body mass gain and regulates proteins related to lipid metabolism in obese rats. In ovariectomized rats, GbE restored the hippocampal and hypothalamic serotonergic system activity, favoring the spontaneous feeding decrement. Considering the promising hypophagic effect of GbE, this study aimed to investigate the effect of a single acute dose on hypothalamic pathways that regulate feeding behavior in male rats. Four-month-old Wistar male rats received either a single acute oral GbE dose (500 mg/kg) or vehicle. Food intake and body mass were measured after 1, 4, 12, and 24 h. Rats were euthanized, and hypothalami were removed for mRNA quantification of anorexigenic (POMC/CART) and orexigenic (AgRP/NPY) neuropeptides, leptin/serotonin receptors (5HT1A, 5HT1B, 5HT2C), and serotonin transporters. We also investigated POMC, 5-HT1B, and 5-HT2C protein levels. A single acute GbE dose induced the hypothalamic POMC, CART, and 5-HT2C gene expression but failed to modify orexigenic effectors. No alterations in food intake, body mass, and hypothalamic protein levels were observed. In summary, the present findings demonstrate the rapid stimulation of pivotal hypothalamic anorexigenic pathways in response to a single GbE administration, reinforcing the GbE hypophagic activity. However, more studies are necessary to evaluate its potential as an appetite modulator.
... Thus, it is extremely necessary to study new therapeutic approaches that can minimize the intensity of menopause consequences. In this context, we hypothesize that Ginkgo biloba extract (GbE) might be useful to treat menopausal women, mainly due to its therapeutic properties already described such as antioxidant, antiinflammatory, and anti-obesogenic, due to its unique chemical composition (flavonoid and terpene lactones) [21][22][23][24]. ...
... (3) improved the insulin signaling/sensitivity; and (4) reduced the adipocyte hypertrophy in white adipose tissue [21,22,25,26]. Moreover, in ovariectomized rats, body weight gain and food intake were attenuated by GbE treatment, likely due to its effect on hypothalamic serotonergic signaling, since it restored the ovariectomy-reduced serotonin levels in the ventromedial hypothalamus as well as the acute anorexigenic response to serotonin impaired by ovariectomy [15]. ...
... Moreover, despite not having evaluated feeding behavior in the current study, we have already demonstrated in a previous study that GbE promoted a hypophagic effect, as it reduced food intake in ovariectomized rats after treatment for 14 days [28]. The treatment protocol and dose of GbE applied was based on previous studies from our group and collaborators that had identified potential effects of this extract on mechanisms involved in the control of energy homeostasis [21,22,25,28,34] and on hippocampal signaling pathways [35][36][37][38]. ...
Since Ginkgo biloba extract (GbE) was reported to improve the hypothalamic serotonergic system of ovariectomized (OVX) rats, the present study aimed to verify the GbE effects on hippocampal oxidative stress, inflammation, and levels of the serotonin transporter (5-HTT), and both the serotonin (5-HT1A, 5-HT1B) and leptin receptors of OVX rats. Two-month-old female Wistar rats had their ovaries surgically removed (OVX) or not (SHAM). After 60 days, OVX rats were gavaged daily with GbE 500 mg kg⁻¹ (OVX+GbE), while SHAM and OVX groups received saline 0.9% (vehicle) for 14 days. Rats were then euthanized, and hippocampi were collected. Both 5-HT1A and 5-HT1B levels were significantly reduced in OVX rats compared to SHAM rats, while 5-HT1A was higher in OVX+GbE rats in comparison to OVX rats. Similarly, LepR levels were increased in OVX+GbE rats compared to OVX rats, reaching similar levels to SHAM rats. Superoxide dismutase activity increased in OVX rats in relation to SHAM rats, which was restored to SHAM levels by GbE treatment. Additionally, GbE significantly increased the glutathione peroxidase activity in comparison to the SHAM group. No differences were observed either in catalase activity or in the levels of 5-HTT, PKCα, TLR-4, NF-κBp50, ERK, and CREB. In summary, our results show a potential effect of GbE on hippocampal pathways involved in feeding behavior, and thus, they suggest that GbE activity might improve menopausal-related hippocampal disorders, offering an alternative therapeutic tool particularly for women to whom hormone replacement therapy may be contraindicated.
Graphical abstract
... Ginkgo biloba is a popular herbal product used to enhance memory and cognitive function and treated the vaso-occlusive disorders [4]. Ginkgo biloba standardized extract (GB) from dried Ginkgo leaves contains 24% flavone glycosides and 6% terpenoids and these constituents showed beneficial pharmacological effects in various experimental disease models like antioxidant, anti-inflammatory, and antiapoptotic activities [16][17][18][19]. ...
Renal injury induced by the chemotherapeutic agent methotrexate (MTX) is a serious adverse effect that has limited its use in the treatment of various clinical conditions. The antioxidant activity of Ginkgo biloba extract (GB) was reported to mitigate renal injury induced by MTX. Our research was conducted to examine the nephroprotective role of GB versus MTX-induced renal injury for the first time through its impact on the regulation of phosphatidylinositol 3-kinase/protein kinase B/ mammalian target of rapamycin (PI3K/Akt/mTOR) signaling together with the renal level of TGF-β mRNA and long non-coding RNA-metastasis-associated lung adenocarcinoma transcript-1 (MALAT1) expression. A group of adult rats was intraperitoneally (ip) injected with MTX 20 mg/kg as a single dose to induce kidney injury (MTX group). The other group of rats was orally administered with GB 60 mg/kg every day for 10 days (GB+ MTX group). The MTX increased the serum creatinine and urea levels, renal TGF-β mRNA and MALAT1 expression, in addition to dysregulation of the PI3K/Akt/mTOR signaling when compared with normal control rats that received saline only (NC group). Moreover, renal damage was reported histopathologically in the MTX group. The GB ameliorated the renal injury induced by MTX and reversed the changes of these biochemical analyses. The involvement of PI3K/Akt/mTOR signaling and downregulation of TGF-β mRNA and MALAT1 renal expressions were firstly reported in the nephroprotective molecular mechanism of GB versus MTX-induced renal injury.
