Pharmacologic treatments in preclinical tinnitus models with special focus on Ginkgo biloba leaf extract EGb 761®

Barth, Stefan; Lehner, Martin D.; Dietz, Gunnar P.H.; Schulze, Holger

doi:10.1016/j.mcn.2021.103669

Cited by 18 publications

(18 citation statements)

References 191 publications

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“…Effects of Ginkgo biloba extracts on tinnitus were described earlier by our group [ 26 , 27 ] and many others (e.g., [ 36 , 37 , 38 ]) and were also summarized and discussed in a recent review [ 11 ]. Briefly, in our earlier animal study regarding the preventive effects of EGb 761 ® [ 26 ], we found that, after 2 weeks of oral application of the extract, the noise-induced hearing loss and the development of a tinnitus percept were significantly reduced already 1 week after the binaural acoustic trauma.…”

Section: Discussionmentioning

confidence: 99%

“…Second, with very few exceptions as in the case of the typewriter tinnitus [ 10 ], no effective treatments that can cure tinnitus have been found. Especially in the case of tonal or narrowband tinnitus, accounting for up to 70% of all cases, several approaches have been evaluated, including but not limited to pharmacological therapy [ 11 ], notched music or noise therapy [ 12 , 13 , 14 ], vagus nerve stimulation [ 15 ], and hyperbaric oxygen therapy [ 16 ]. Most of these approaches did not show strong effects on the tinnitus percept, at least in chronic cases.…”

Section: Introductionmentioning

confidence: 99%

“…One candidate for such a pharmaceutical product is the clinically and non-clinically tested Ginkgo biloba leaf extract EGb 761 ® (for a review, see [ 11 ]). It has already shown significant effects against the development of hearing loss and tinnitus in either preventive or curative approaches in animal models as assessed with hearing threshold measurements and behavioral tests [ 26 , 27 ].…”

Section: Introductionmentioning

confidence: 99%

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Preventive Effects of Ginkgo-Extract EGb 761® on Noise Trauma-Induced Cochlear Synaptopathy

Tziridis

Schulze

2022

Nutrients

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Noise trauma-induced loss of ribbon synapses at the inner hair cells (IHC) of the cochlea may lead to hearing loss (HL), resulting in tinnitus. We are convinced that a successful and sustainable therapy of tinnitus has to treat both symptom and cause. One of these causes may be the mentioned loss of ribbon synapses at the IHC of the cochlea. In this study, we investigated the possible preventive and curative effects of the Ginkgo biloba extract EGb 761® on noise-induced synaptopathy, HL, and tinnitus development in Mongolian gerbils (Meriones unguiculatus). To this end, 37 male animals received EGb 761® or placebo orally 3 weeks before (16 animals) or after (21 animals) a monaural acoustic noise trauma (2 kHz, 115 dB SPL, 75 min). Animals’ hearing thresholds were determined by auditory brainstem response (ABR) audiometry. A possible tinnitus percept was assessed by the gap prepulse inhibition acoustic startle reflex (GPIAS) response paradigm. Synaptopathy was quantified by cochlear immunofluorescence histology, counting the ribbon synapses of 15 IHCs at 11 different cochlear frequency locations per ear. We found a clear preventive effect of EGb 761® on ribbon synapse numbers with the surprising result of a significant increase in synaptic innervation on the trauma side relative to placebo-treated animals. Consequently, animals treated with EGb 761® before noise trauma did not develop a significant HL and were also less affected by tinnitus compared to placebo-treated animals. On the other hand, we did not see a curative effect (EGb 761® treatment after noise trauma) of the extract on ribbon synapse numbers and, consequently, a significant HL and no difference in tinnitus development compared to the placebo-treated animals. Taken together, EGb 761® prevented noise-induced HL and tinnitus by protecting from noise trauma-induced cochlear ribbon synapse loss; however, in our model, it did not restore lost ribbon synapses.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Preventive Effects of Ginkgo-Extract EGb 761® on Noise Trauma-Induced Cochlear Synaptopathy

Tziridis

Schulze

2022

Nutrients

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“…Natural plant extracts have traditionally been used as medicinal ingredients for various diseases (Guerra et al, 2018). Ginkgo biloba Leaf Extract (GBE) is a natural drug with few chemical side effects known to be effective in improving brain function and expanding blood vessels (Tian et al, 2019a;Barth et al, 2021). GBE contains a substance called flavonoid, which acts as an inhibitor of plateletactivating factor (PAF) and has various medicinal effects as an infectious phospholipid.…”

Section: Discussionmentioning

confidence: 99%

“…Ginkgo biloba Leaf Extract (GBE) has anti-oxidant and anticancer effects by impacting the survival rate of melanoma cells (Barth et al, 2021;Liu et al, 2021). In recent studies,…”

Section: Introductionmentioning

confidence: 99%

Ginkgo biloba Leaf Extract Regulates Cell Proliferation and Gastric Cancer Cell Death

et al. 2022

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Ginkgo biloba Leaf Extract (GBE) is an extract from leaves of the Ginkgo biloba tree, widely used as a health supplement. GBE can inhibit the proliferation of several types of tumor cell. Although it is known to have anti-cancer effects in breast cancer and skin cancer, research related to gastric cancer is still insufficient. Based on results showing anti-cancer effects on solid cancer, we aimed to determine whether GBE has similar effects on gastric cancer. In this study, the anticancer effect of GBE in gastric adenocarcinoma was investigated by confirming the cell proliferation inhibitory effect of AGS cells. We also evaluated whether GBE regulates expression of the tumor suppressor protein p53 and Rb. GBE has apoptotic effects on AGS cells that were confirmed by changes in anti-apoptosis protein Bcl-2, Bcl-xl and pro-apoptosis protein Bax levels. Wound healing and cell migration were also decreased by treatment with GBE. Furthermore, we verified the effects of GBE on mitogenic signaling by investigating AKT target gene expression levels and revealed downregulated Sod2 and Bcl6 expression. We also confirmed that expression of inflammation-related genes decreased in a time-dependent manner. These results indicate that GBE has an anti-cancer effect on human gastric cancer cell lines. Further research on the mechanism of the anti-cancer effect will serve as basic data for possible anti-cancer drug development.

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Identification and quantification of the antioxidants in Ginkgo biloba leaf

Hu,

Wang,

Deng

et al. 2024

Biomedical Chromatography

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The antioxidant activity of Ginkgo biloba leaf (GBL) extract is closely related to its efficacy against various diseases; however, the antioxidant activities of the specific constituents of GBL remain unclear. In this study, 194 GBL constituents were identified using ultra‐performance liquid chromatography‐quadrupole‐time‐of‐flight mass spectrometry, including 97 flavonoids, 37 terpenoids, 29 lignans, 19 carboxylic acids, 5 alkylphenolic acids, 5 alkylphenols, and 2 other compounds. The cleavage rules of the main constituents of GBL were dissected in detail. The 36 GBL constituents with high antioxidant activity were subsequently discovered using the oxygen radical absorbance capacity assay, including 30 flavonoids and six carboxylic acids. Finally, an HPLC analysis method was established to determine the content of the nine major antioxidants in the three batches of GBL. Among them, kaempferol 3‐O‐β‐D‐(6″‐p‐coumaroyl) glucopyranosyl‐(1‐2)‐α‐L‐rhamnopyranoside, kaempferol‐3‐O‐rutinoside, and rutin exhibited high antioxidant activity and were found in significant amounts in GBL, with concentrations greater than 0.7 mg/g. These results provide an important reference for the development of pharmaceuticals and health products containing GBL.

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Pharmacologic treatments in preclinical tinnitus models with special focus on Ginkgo biloba leaf extract EGb 761®

Cited by 18 publications

References 191 publications

Preventive Effects of Ginkgo-Extract EGb 761® on Noise Trauma-Induced Cochlear Synaptopathy

Preventive Effects of Ginkgo-Extract EGb 761® on Noise Trauma-Induced Cochlear Synaptopathy

Ginkgo biloba Leaf Extract Regulates Cell Proliferation and Gastric Cancer Cell Death

Identification and quantification of the antioxidants in Ginkgo biloba leaf

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