The Potency of Ginkgo Biloba in Treating Tinnitus: A Review

Extracts of Ginkgo biloba leaves are used for medicinal purposes for at least 5000 years in China. More recently Ginkgo biloba extracts have been used in Western countries. In the USA, Canada and the UK extracts are widely available as nonprescription food supplements. In France and Germany, a standardized dry leaf extract is registered as a drug and is commonly prescribed for. Several studies have been conducted to measure the usefulness and properties of Ginkgo Biloba in connection with the treatment of Tinnitus. This literature review aims to identify the components and the mechanism of action of Ginkgo Biloba in the treatment of tinnitus. The articles selected were all published within the past five years from PubMed. 11 articles were obtained and were included in the review. Based on the articles, The most important active chemical compounds in Ginkgo Biloba are flavonoids (ginkgo-flavone glycosides) and terpenoids (ginkgolides A, B, C, J, and bilobalide). Gingko Biloba has vasoregulatory effect, antagonism of platelet activator factor, antioxidant activity, enhance neuroplasticity and inflammatory. In conclusion, Ginkgo Biloba demonstrated effectiveness in the treatment of tinnitus, through the significant improvement in self-perception of tinnitus loudness and severity.


Introduction
Tinnitus has defined a perception of sound that is heard without an external auditory stimulus. It is described as a ringing, hissing, buzzing or wheezing sound due to some pathologic activity that affects the auditory pathway at some point. The brain thus interpreted it as a sound. Tinnitus may be defined variously, as a sound perceived for more than 5 min at a time in absence of any external acoustical or electrical stimulation of the ear. Sound percieved after high intensity noise, and psychological disease are not included. However, tinnitus can be objective and subjective. Objective tinnitus is defined as tinnitus that can be heard by both the examiner and the examinee. Subjective is defined as a tinnitus that only can be heard by the examinee. Both types of tinnitus, objective or subjective, can cause severe mental and physical impairments thus impair the persons quality of life. Symptoms of depression and anxiety are highly prevalent in patients with tinnitus; comorbidity rates between 50 and 90% have been reported from most studies. 1,2,7,11 The prevalence of tinnitus is about 3-30% in the population and the prevalence is increased with age.
Tinnitus is a major health problem, with an estimated prevalence of 9.6% and a 10-year cumulative incidence rate of 12. 7%

Type Causes
Ear disorders More than 90% of tinnitus cases are caused by the ear disorders. Earwax, otitis media, trauma, acoustic trauma, atmospheric pressure changes and direct blows to the ear can also cause tinnitus. Tinnitus is commonly observed in presbycusis and is highly frequent Cardiovascular causes Cardiovascular causes are the second most common causes of tinnitus. Approximately, on third of patients with severe tinnitus are suffering from one or more cardiovascular disorders. 75% of these patients suffer from hypertension and their tinnitus is often treated when their hypertension is treated.

Neurological disorders or head injuries
Neurological disorders or trauma, including skull fractures or injuries of any type of blunt head lead to tinnitus in 5 to 10% of cases. Skull fractures can cause tinnitus and sensory-nerve hearing loss usually towards high frequencies. Also, in the case of the rupture of ear bones. Conductive hearing loss will be seen. Tinnitus is caused following the damage caused by the intense back and forth shaking of the head in traffic accidents, usually a few days to a few weeks after accident.

Pharmacological side effects
Over 10% of subjective tinnitus cases, especially in elderly patients are due to the side effect of drugs, the most important of which is aspirin.
Other drugs include non-steroidal, anti-inflammatory drugs, antibiotics, particularly aminoglycosides, antidepressants, and tranquilizers can also cause tinnitus.

Dental diseases
Dental diseases or nay temporomandibular disorder could exacerbate tinnitus. In these cases, the patients feel fulness or pressure in the ear and sensitivity in temporomandibular and mandibular joints.

Metabolic disorders
Metabolic disorders are considered as a relatively uncommon cause of tinnitus. Hyperthyroidism causes annoying and problematic tinnitus in 4% of cases. Vitamin A deficiency has also been reported as the cause of tinnitus but it is very rare.
Psychological causes Psychological factors may cause or aggravate tinnitus. Also, stress exacerbates the tinnitus severity.
Objective tinnitus This type of tinnitus is heard with or without the use of the phone by the doctor and has vascular, mechanical or neoplastic's muscle origin.
Idiopathic tinnitus Various causes are involved in idiopathic tinnitus. One of them is reactive oxygen species (ROS). high serum values of ROS related to the idiopathic tinnitus has been detected. Evaluated ROS concentrations can lead to cytotoxic effects that affect neurons and ciliated cells in the inner ear. Besides, it can increase the glutamate as the excitatory neurotransmitter and lead to inflammation and necrosis of dendrites of afferent cochlear Corti organ cells by stimulating production of free radicals.

Methods
PubMed were used as the searching engine in this study. The searching was conducted up to Aug 8, 2021 using the keywords "Ginkgo Biloba" and "Tinnius." Articles selected were all published within the past five years. Duplicate articles were excluded.
From PubMed 10 results were obtained and were included in the review.

Result and Discussion
Based on the result from the review studies, we have found several pertinent information about Gingko Biloba in regards to the treatment tinnitus.

Tinnitus and Ginkgo Biloba
There has been an increase of interest approach

Mechanism of action of Gingko Biloba
The mechanism of action of Gingko biloba in decreasing the symptom of tinnitus are as follow. 1

Vasoregulatory effect
A vasoregulatory effect is one of the most important action for Gingko Biloba.

Enhancement of neuronal plasticity
Enhancement of neuronal plasticity including increased long-term potentiation, spine density, neuritogenesis and neurogenesis, as shown in preclinical reports. 1

Anti-inflammatory effect
Anti-inflammatory effects and protective actions against brain damage, possibly through its terpenoids and ginkgolides. The Ginkgo biloba leaf extract has been shown to reduce the level of cytokines and inflammatory factors such as tumor necrosis factor-alpha (TNF-R), interleukin 6 (Il-6),