A critical review of current technologies used to reduce ginkgotoxin, ginkgotoxin-5′-glucoside, ginkgolic acid, allergic glycoprotein, and cyanide in Ginkgo biloba L. seed

The Ginkgo biloba has astonished scholars globally with enormous bioactives, with sales exceeding $10 billion since 2017. The Ginkgo biloba seed (GBS) is an essential part of culinary culture. Nevertheless, toxins in fresh Ginkgo biloba seed (GBS) have limited GBSs’ daily consumption. Ginkgotoxin and ginkgotoxin-5-glucoside cause poisoning, tonic-clonic convulsions, and neurotoxic effects.
Ginkgolic acid causes cytotoxicity and allergies. Allergic glycoprotein in GBS causes nausea, seizures, dyspnea, mydriasis, vomiting, and bellyache. The amygdalin-derived hydrocyanic acid cause dizziness, vomiting, cramping, and sleeping disorders. Food products are frequently exposed to various processing techniques to increase food safety and functionality.
As a result, this review focused on the technologies that have been used to minimize toxins in GBS. In addition, a comparison of these techniques was made based on their benefits, drawbacks, feasibility, pharmacological activities, and future direction or opportunities to improve current ones were provided.

The Mechanism of Action of Ginkgolic Acid (15:1) against Gram-Positive Bacteria Involves Cross Talk with Iron Homeostasis

With the increasing reports of community-acquired and nosocomial infection caused by multidrug-resistant Gram-positive pathogens, there is an urgent need to develop new antimicrobial agents with novel antibacterial mechanisms.
Here, we investigated the antibacterial activity of the natural product ginkgolic acid (GA) (15:1), derived from Ginkgo biloba, and its potential mode of action against the Gram-positive bacteria Enterococcus faecalis and Staphylococcus aureus. The MIC values of GA (15:1) against clinical E. faecalis and S. aureus isolates from China were ≤4 and ≤8 μg/mL, respectively, from our test results. Moreover, GA (15:1) displayed high efficiency in biofilm formation inhibition and bactericidal activity against E. faecalis and S. aureus.
During its inhibition of the planktonic bacteria, the antibacterial activity of GA (15:1) was significantly improved under the condition of abolishing iron homeostasis. When iron homeostasis was abolished, inhibition of planktonic bacteria by GA (15:1) was significantly improved.
This phenomenon can be interpreted as showing that iron homeostasis disruption facilitated the disruption of the functions of ribosome and protein synthesis by GA (15:1), resulting in inhibition of bacterial growth and cell death. Genetic mutation of ferric uptake regulator (Fur) led to GA (15:1) tolerance in in vitro-induced resistant derivatives, while overexpression of Fur led to increased GA (15:1) susceptibility. Additionally, GA (15:1) significantly decreased the bacterial loads of S. aureus strain USA300 in the lung tissues of mice in a pneumonic murine model.
Conclusively, this study revealed an antimicrobial mechanism of GA (15:1) involving cross talk with iron homeostasis against Gram-positive pathogens. In the future, the natural product GA (15:1) might be applied to combat infections caused by Gram-positive pathogens.
IMPORTANCE The increasing emergence of infectious diseases associated with multidrug-resistant Gram-positive pathogens has raised the urgent need to develop novel antibiotics. GA (15:1) is a natural product derived from Ginkgo biloba and possesses a wide range of bioactivities, including antimicrobial activity.
However, its antibacterial mechanisms remain unclear. Our current study found that the function of ferric uptake regulator (Fur) was highly correlated with the antimicrobial activity of GA (15:1) against E. faecalis and that the antibacterial activity of GA (15:1) could be strengthened by the disruption of iron homeostasis. This study provided important insight into the mode of action of GA (15:1) against Gram-positive bacteria and suggested that GA (15:1) holds the potential to be an antimicrobial treatment option for infection caused by multidrug-resistant Gram-positive pathogens.

Ginkgolic Acid (GA) Inhibits the Growth of OCa by Inhibiting lncRNA MALAT1/JAK2 Axis

Objective: We aimed to observe the impact of ginkgolic acid (GA) on the proliferation and metastasis ability of ovarian cancer (OCa) cells and to further explore whether GA affects the malignant progress of OCa via regulating the lncRNA MALAT1/JAK2 axis.
Methods: OCa cells SKOV3 and CAOV3 were administered with 1 ng/ml GA, 5 ng/ml GA, 10 ng/ml GA, 20 ng/ml GA, and DSMO as control, respectively. The cell proliferation and migration ability of the abovementioned cells in each group were measured by CCK-8 test and Transwell experiments.
The expression levels of lncRNA MALAT1 and JAK2 protein were examined by qRT-PCR and western blot, respectively. Subsequently, in OCa cells treated with GA, lncRNA MALAT1 overexpression vector was transfected to continue to detect the proliferation activity and migration ability of each treatment group.
Finally, the regulation of GA on activity of lncRNA MALAT1/JAK2 axis in OCa cells was further explored in nude mice.
Results: Our data showed that the proliferation inhibition rate of cells at each ginkgolic acid concentration was higher than that of the control group (P < 0.05), suggesting that GA has an inhibitory influence on the proliferation of OCa cells, in a dose-dependent way.
GA was able to inhibit the proliferation rate and migration ability of OCa cells. Administration of ginkgolic acid downregulated the levels of lncRNA MALAT1 and JAK2 protein.
Overexpression of lncRNA MALAT1 partially reversed the inhibited OCa proliferative capacity caused by GA treatment.
Consistent with the results observed in vitro, we also found that the OCa tumor weight and volume of nude mice injected with lncRNA MALAT1 overexpression vector were enhanced and JAK2 protein level increased remarkably in comparison to the ginkgolic acid group.
Conclusions: In summary, GA may exert its inhibitory effect on the proliferative and migratory capacities of OCa cells through suppressing the activity of lncRNA MALAT1/JAK2 axis.

Anti-Cancer Properties of Ginkgolic Acids in Human Nasopharyngeal Carcinoma CNE-2Z Cells via Inhibition of Heat Shock Protein 90

Ginkgo biloba L. has been used in traditional Chinese medicine (TCM) for thousands of years. However, the anti-cancer properties of ginkgolic acids (GAS) isolated from G. biloba have not been investigated in human nasopharyngeal carcinoma cells. In this study, GAS exhibited an inhibitory effect on the ATPase activity of heat shock protein 90 (Hsp90) and anti-proliferative activities against four human cancer cell lines, with IC50 values ranging from 14.91 to 23.81 μg·mL-1.

Ginkgolic acid

M75004 EpiGentek 5 mg 841.26 EUR

Ginkgolic Acid

HY-N0077 MedChemExpress 10mg 482.4 EUR

Ginkgolic acid II

TB0814-0025 ChemNorm 10mg 325.2 EUR

Ginkgolic acid I

TB0816-0025 ChemNorm 10mg 223.2 EUR

Ginkgolic Acid C15:1

C3421-1 ApexBio 1 mg 141.6 EUR

Ginkgolic Acid C15:1

C3421-10 ApexBio 10 mg 632.4 EUR

Ginkgolic Acid C15:1

C3421-5 ApexBio 5 mg 408 EUR

Ginkgolic acid C15:1

9523-25 Biovision each 966 EUR

Ginkgolic acid C15:1

9523-5 Biovision each 288 EUR

Ginkgolic acid C17:1

HY-N2116 MedChemExpress 10mg 688.8 EUR

Ginkgolic Acid (C13:0)

HY-N0078 MedChemExpress 10mg 456 EUR

Ginkgolic Acid C17 2

TBW01789 ChemNorm 20mg Ask for price

Ginkgolide B

N1879-20 ApexBio 20 mg 129.6 EUR

Ginkgolide A

N1900-20 ApexBio 20 mg 268.8 EUR

Ginkgolide A

N1900-5.1 ApexBio 10 mM (in 1mL DMSO) 135.6 EUR

Ginkgolide C

N1908-20 ApexBio 20 mg 268.8 EUR

Ginkgolide J

N2385-20 ApexBio 20 mg 338.4 EUR

Ginkgolide B

E1KS1343 EnoGene 25mg 390 EUR

Ginkgolide K

HY-N4176 MedChemExpress 10mM/1mL 368.4 EUR

Ginkgolide A

HY-B0355 MedChemExpress 50mg 349.2 EUR

Ginkgolide B

HY-N0784 MedChemExpress 10mg 118.8 EUR

Ginkgolide C

HY-N0785 MedChemExpress 10mM/1mL 214.8 EUR

Ginkgolide J

HY-N0786 MedChemExpress 10mg 688.8 EUR

Ginkgolide C

GP0779-10 Glentham Life Sciences 10 150.8 EUR

Ginkgolide C

GP0779-50 Glentham Life Sciences 50 457.7 EUR

Ginkgolide B

GP5638-10 Glentham Life Sciences 10 91.6 EUR
In vivo experiments confirmed that GAS inhibited tumor growth in CNE-2Z cell-xenografted nude mice with low hepatotoxicity. We further demonstrated that GAS suppressed migration and invasion and induced the apoptosis of CNE-2Z cells by inducing the degradation of Hsp90 client proteins (MMP-2, MMP-9, Her-2, c-Raf, Akt, and Bcl-2).
Together, GAS are new Hsp90 inhibitors by binding to Hsp90 (hydrogen bond and hydrophobic interaction). Thus, GAS from G. biloba might represent promising Hsp90 inhibitors for the development of anti-nasopharyngeal carcinoma agents.

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