Ginkgo biloba leaves (GBLs) contain high phytoconstituents, but ginkgolic acids (GAs, the main toxic compound in GBLs) have limited its applications. Processing Ginkgo biloba dark tea (GBDT) using fixation technology could decrease the toxic compounds; retain flavonoids, ginkgolides, and bilobalide; and improve the product quality. For the first time, various thermal fixations (hot air fixation [HAF], iron pot fixation [IPF], and boiled water fixation [BWF]) followed by rolling, fermentation, and drying were applied to produce GBDT. A comprehensive analysis of the toxicants (GAs), main bioactive compounds (ginkgolides and bilobalide, flavonoids, antioxidants, and phenolic profiles), and product qualities (moisture content, reducing sugar [RS], free amino acids [FAAs], enzyme activity, color properties, antioxidant capacity, etc.) were evaluated. The results revealed that thermal fixations BWF and HAF significantly reduced the GA contents (41.1%-34.6%). Most terpene lactones showed significant differences in control, IPF, and HAF. The HAF had lower total flavonoid content (TFC) than BWF and IPF. The control group (unfixated) had the highest toxic components (GA), terpene trilactones, and TFC compared with various fixations. Adding different fixations to rolling, fermentation, and drying had various impacts on GBDT, and principal component analysis supported the results. Among four thermal fixations, HAF yielded the best results in RS, FAA, total phenolic content, and antioxidant activities, while IPF had the highest TFC. BWF had the lowest content for GA. In conclusion, HAF (6) was chosen as the best technique for producing GBDT since it preserved GBDT\'s bioactive components while lowering its toxic components.

Nanomedicine for treating post-viral infectious disease syndrome is at an emerging stage. Despite promising results from preclinical studies on conventional antioxidants, their clinical translation as a therapy for treating post-COVID conditions remains challenging. The limitations are due to their low bioavailability, instability, limited transport to the target tissues, and short half-life, requiring frequent and high doses. Activating the immune system during coronavirus (SARS-CoV-2) infection can lead to increased production of reactive oxygen species (ROS), depleted antioxidant reserve, and finally, oxidative stress and neuroinflammation. To tackle this problem, we developed an antioxidant nanotherapy based on lipid (vesicular and cubosomal types) nanoparticles (LNPs) co-encapsulating ginkgolide B and quercetin. The antioxidant-loaded nanocarriers were prepared by a self-assembly method via hydration of a lyophilized mixed thin lipid film. We evaluated the LNPs in a new in vitro model for studying neuronal dysfunction caused by oxidative stress in coronavirus infection. We examined the key downstream signaling pathways that are triggered in response to potassium persulfate (KPS) causing oxidative stress-mediated neurotoxicity. Treatment of neuronally-derived cells (SH-SY5Y) with KPS (50 mM) for 30 min markedly increased mitochondrial dysfunction while depleting the levels of both glutathione peroxidase (GSH-Px) and tyrosine hydroxylase (TH). This led to the sequential activation of apoptotic and necrotic cell death processes, which corroborates with the crucial implication of the two proteins (GSH-Px and TH) in the long-COVID syndrome. Nanomedicine-mediated treatment with ginkgolide B-loaded cubosomes and vesicular LNPs showed minimal cytotoxicity and completely attenuated the KPS-induced cell death process, decreasing apoptosis from 32.6% (KPS) to 19.0% (MO-GB), 12.8% (MO-GB-Quer), 14.8% (DMPC-PEG-GB), and 23.6% (DMPC-PEG-GB-Quer) via free radical scavenging and replenished GSH-Px levels. These findings indicated that GB-LNPs-based nanomedicines may protect against KPS-induced apoptosis by regulating intracellular redox homeostasis.

The review presents an analysis of experimental data on the study of neurobiological effects of ginkgolide B, which may find application in the therapy of Alzheimer\'s disease (AD). Ginkgolide B is a diterpene trilactone isolated from the leaves of the relict woody plant Ginkgo biloba L., which has been used for thousands of years in traditional Chinese medicine as a neuroprotective agent. In recent years, this compound has attracted attention because of its wide range of neurobiological effects. The neuroprotective effect of ginkgolide B on brain neurons when exposed to various neurotoxins has been established. This compound has also been shown to effectively protect neurons from the effects of beta-amyloid. Studies have revealed the ability of ginkgolide B to reduce microglia activity and regulate neurotransmitter release. In vivo experiments have shown that this substance significantly increases the expression of brain-derived neurotrophic factor (BDNF) and improves cognitive functions, including memory and learning. It is concluded that ginkgolide B, apparently, may find application in the future as a multi-targeted agent of complex therapy of AD.
В обзоре представлен анализ экспериментальных данных по исследованию нейробиологических эффектов гинкголида B, которые могут найти применение в терапии болезни Альцгеймера (БА). Гинкголид B — это дитерпеновый трилактон, выделенный из листьев реликтового древесного растения гинкго двулопастного (Ginkgo biloba L.), которое в течение тысячелетий используется в традиционной китайской медицине. В последние годы это соединение привлекает внимание из-за широкого спектра нейробиологических эффектов. Установлено нейропротективное действие гинкголида B на нейроны головного мозга при воздействии различных нейротоксинов. Показано, что данное соединение также эффективно защищает нейроны от воздействия бета-амилоида. Исследования выявили способность гинкголида B снижать активность микроглии и регулировать выделение нейромедиаторов. В экспериментах in vivo показано, что данное вещество значительно повышает экспрессию нейротрофического фактора мозга (BDNF), а также улучшает когнитивные функции, включая память и способность к обучению. Делается вывод, что гинкголид B, по-видимому, может найти применение в будущем в качестве многоцелевого средства комплексной терапии БА.

Four undescribed ginkgolides, including two rare sesquiterpene ginkgolides (compounds 1 and 2) and two diterpenoid ginkgolides (compounds 3 and 4), were isolated from Ginkgo biloba L. The structures of these four ginkgolides were identified based on extensive spectroscopic analysis, DP4+ probability analysis and X-ray diffraction. Compounds 1 and 2 exhibited excellent antiplatelet aggregation activities with IC50 values of 1.20 ± 0.25 and 4.11 ± 0.34 μM, respectively.

The glymphatic system plays a crucial role in maintaining optimal central nervous system (CNS) function by facilitating the removal of metabolic wastes. Aquaporin-4 (AQP4) protein, predominantly located on astrocyte end-feet, is a key pathway for metabolic waste excretion. β-Dystroglycan (β-DG) can anchor AQP4 protein to the end-feet membrane of astrocytes and can be cleaved by matrix metalloproteinase (MMP)-9 protein. Studies have demonstrated that hyperglycemia upregulates MMP-9 expression in the nervous system, leading to neuropathic pain. Ginkgolide B (GB) exerts an inhibitory effect on the MMP-9 protein. In this study, we investigated whether inhibition of MMP-9-mediated β-DG cleavage by GB is involved in the regulation of AQP4 polarity within the glymphatic system in painful diabetic neuropathy (PDN) and exerts neuroprotective effects. The PDN model was established by injecting streptozotocin (STZ). Functional changes in the glymphatic system were observed using magnetic resonance imaging (MRI). The paw withdrawal threshold (PWT) was measured to assess mechanical allodynia. The protein expressions of MMP-9, β-DG, and AQP4 were detected by Western blotting and immunofluorescence. Our findings revealed significant decreases in the efficiency of contrast agent clearance within the spinal glymphatic system of the rats, accompanied by decreased PWT, increased MMP-9 protein expression, decreased β-DG protein expression, and loss of AQP4 polarity. Notably, GB treatment demonstrated the capacity to ameliorate spinal cord glymphatic function by modulating AQP4 polarity through MMP-9 inhibition, offering a promising therapeutic avenue for PDN.

This research delves into the effectiveness of Ginkgolide B (GB), a compound from Ginkgo biloba, in combating cell death caused by glaucoma, with a focus on mitochondrial impairment and the mitochondrial permeability transition pore (mPTP). Utilizing models of high intraocular pressure and in vitro glaucoma simulations, the study investigates GB\'s impact on retinal progenitor cells (RPCs) under oxygen-glucose deprivation/reperfusion (OGD/R) and in a rat glaucoma model. The study methodologies included apoptosis assessment, apoptotic marker analysis via Western blot, and mitochondrial structure and function evaluation. The findings reveal that GB notably decreases apoptosis in RPCs exposed to OGD/R in vitro, and reduces ischemia-reperfusion damage in vivo. GB\'s protective role is attributed to its ability to preserve mitochondrial integrity, maintain membrane potential, regulate calcium levels, and inhibit mPTP opening. These results underscore GB\'s potential as a therapeutic agent for acute primary angle-closure glaucoma, highlighting its capability to alleviate mitochondrial damage and apoptosis in RPCs and retinal nerve fiber layer cells.

BACKGROUND: Ginkgo biloba, as the most widely available medicinal plant worldwide, has been frequently utilized for treat cardiovascular, cerebrovascular, diabetic and other diseases. Due to its distinct pharmacological effects, it has been broadly applications in pharmaceuticals, health products, dietary supplements, and so on. Ginkgolide C (GC), a prominent extract of Ginkgo biloba, possesses potential in anti-inflammatory and anti-oxidant efficacy.
OBJECTIVE: To determine whether GC mitigated the progressive degeneration of articular cartilage in a Monosodium Iodoacetate (MIA)-induced osteoarthritis (OA) rat model by inhibiting the activation of the NLRP3 inflammasome, and the specific underlying mechanisms.
METHODS: In vivo, an OA rat model was established by intra-articular injection of MIA. The protective effect of GC (10 mg/kg) on articular cartilage was evaluated. Application of ATDC5 cells to elucidate the mechanism of the protective effect of GC on articular cartilage. Specifically, the expression levels of molecules associated with cartilage ECM degrading enzymes, OS, ERS, and NLRP3 inflammasome activation were analyzed.
RESULTS: In vivo, GC ameliorated MIA-induced OA rat joint pain, and exhibited remarkable anti-inflammatory and anti- ECM degradation effects via inhibition of the activation of NLRP3 inflammasome, the release of inflammatory factors, and the expression of matrix-degrading enzymes in cartilage. Mechanically, GC inhibited the activation of NLRP3 inflammasome by restraining ROS-mediated p-IRE1α and activating Nrf2/NQO1 signal path, thereby alleviating OA. The ROS scavenger NAC was as effective as GC in reducing ROS production and inhibiting the activation of NLRP3 inflammasome.
CONCLUSIONS: GC have exerted chondroprotective effects by inhibiting the activation of NLRP3 inflammasome.

OBJECTIVE: To systemically evaluate the efficacy and safety of diterpene ginkgolides meglumine injection (DGMI) on cerebral infarction (CI).
METHODS: Comprehensively collect randomized controlled trials of DGMI in the treatment of CI in 7 databases including Embase, PubMed, the Cochrane Library, the China National Knowledge Infrastructure Database, the WanFang Database, the China Science and Technology Journal Database, and the China Biology Medicinedisc as of January 2023. The studies were screened according to the inclusion and exclusion criteria and evaluated according to the criteria recommended by the Cochrane Handbook, then RevMan 5.3, Stata 12.0 software were used for Meta-analysis.
RESULTS: A total of 22 randomized controlled trials with 2194 patients were included. Meta analysis showed that: the total effective rate of treatment (relative risk = 1.29, 95% confidence interval (1.21, 1.38), P < .001), National Institute of Health stroke scale score, Barthel index and Modified Rankin Scale were better in DGMI group than in Conventional Western Medicine Treatment group. The included studies reported 42 adverse events, 25 of which belonged to DGMI groups.
CONCLUSIONS: Available evidence suggested that DGMI can significantly improve the clinical efficiency in the treatment of CI. DGMI is an ideal treatment for CI, which has high clinical application value.

OBJECTIVE: To evaluate the efficacy and safety of Ginkgolide Meglumine Injection (GMI) combined with Butylphthalide in the treatment of Acute Ischemic Stroke (AIS), and provide reference for rational clinical medication.
METHODS: PubMed, Embase, Web of science, CNKI, Wanfang, VIP and other databases were searched for published studies on the treatment of AIS with GMI combined with Butylphthalide in both Chinese and English. The search period was from the establishment of the database to July 2023. The included studies that met the inclusion criteria were analyzed using RevMan 5.3 software for Meta-analysis.
RESULTS: A total of 25 studies involving 2362 patients (experimental group = 1182, control group = 1180) were included. The results of meta-analysis showed that the overall effective rate of the experimental group was significantly higher than that of the control group [RR = 1.21, 95% CI (1.16, 1.26), P< 0.00001]. In addition, compared with the control group, the experimental group showed significant improvement in NIHSS score [SMD = -1.59, % CI (-2.00-1.18), P< 0.00001] and ADL score [SMD = 2.12, 95% CI (1.52, -2.72), P<0.00001], significant decrease in CRP [SMD = -2.24, 95% CI (-3.31, -1.18), P<0.0001] and TNF-α [SMD = -2.74, 95% CI (-4.45, -1.03), P< 0.005] levels, and improvement in plasma viscosity [SMD = -0.86, 95% CI (-1.07, -0.66), P< 0.00001]. However, the influence on homocysteine level remains inconclusive. Furthermore, there was no significant difference in the incidence of adverse reactions between the two groups [SMD = 0.95, 95% CI (0.71, 1.28), P> 0.05].
CONCLUSIONS: GMI combined with Butylphthalide shows good clinical application effects and good safety in the treatment of AIS. However, more large-sample, multicenter, randomized controlled are needed to confirm these findings.

Ginkgolides are receptor antagonist of platelet activating factor with great clinical prospect, but its application is limited by its low solubility, short half-life and poor alkaline environment stability. It is difficult to solve these problems with a single drug delivery system. In this study, supersaturated self-nanoemulsifying gastric floating tablets of ginkgolides were developed through the combination of solid supersaturated self-nanoemulsifying drug delivery system (solid S-SNEDDS) and gastric retentive floating drug delivery system (GFDDS) to solve these problems of ginkgolides. Solid S-SNEDDS was prepared by D-optimal mixture design, normalization method and single factor experiment. The properties of solid-S-SNEDDS were studied by TEM, PXRD, FT-IR, SEM and in vitro drug release profile. Then, the optimal formulation of stomach floating tablet was obtained through single factor experiment and center composite design, followed by the study of in vitro release, model and mechanism of release, in vitro buoyancy and kinetics of erosion and swelling. PXRD and FT-IR showed that the drug in solid S-SNEDDS existed in an amorphous manner and formed hydrogen bond with excipients. The results showed that the cumulative release of GA and GB in the optimal tablets was 96.12% and 92.57% higher than the simple tablets within 12 h. The release mechanism of the tablet was skeleton erosion and drug diffusion. In 12 h, the optimal tablets can float stably in vitro and release the drug at a constant rate, with a cumulative release of more than 80%. In summary, the combination of SNEDDS and GFDDS is a promising means to solve the problems of ginkgolides.