An organism's immune system is a well-developed system that defends the body against harmful particles such as pathogens, damaged cells, and toxic compounds.1 It produces several cells that can detect such non-self particles. These cells are capable of eliciting an immune response against non-self particles to prevent them from infiltrating or destroying the body.2 When immune response gets out of control it elucidates devastating effects on the body. Such effects are generally considered as inflammatory response or auto-immune response. Many drug therapies have been developed to encounter such responses in our body. Apart from drug therapy researchers are also looking for certain herbs which have putative ability in fighting against such immune responses.
Here we will be describing one inflammatory response called Tinnitus. It is an effect related to hearing for which the treatment of a herb known as Ginkgo biloba was introduced. It has shown to have anti-inflammatory effects and protection against brain damage.3 Because of such mechanisms, Ginkgo biloba, a herb, has come into the picture of the research world.
One of the complex immune responses includes Inflammation. It is a defense mechanism to eliminate compounds that are intended to harm the body. Several immune cells are involved in this response. There are two types of the inflammatory response:
- Acute Inflammatory Response
- Chronic Inflammatory Response
Damaged cells, infections, abnormal cells, and other infectious factors attract immune cells to the site of injury. These encountered cells become activated and produce cytokines, which trigger an inflammatory response. Cytokines are proteins that cells secrete when they come into contact with certain external factors. Pro-inflammatory Cytokines for example; IL-1β, IL-6, and TNF-⍺ are involved in inflammatory responses.4 These cytokines aid in the removal of infectious particles, decreasing injury. These compounds are potential biomarkers in the diagnosis, prognosis, and treatment of diseases. Some viral agents can bypass defense mechanisms and trigger chronic reactions. IFN-γ and TNF-⍺ are two cytokines that play a key role in the development of chronic inflammation.5 When acute responses go uncontrolled, they become chronic, leading to Chronic Inflammatory Diseases.
TNF-⍺ - a Therapeutic Target :
TNF-⍺ is a cytokine that the immune system uses to signal cells. When immune cells (macrophages) detect an infection, they release TNF-⍺ as part of the inflammatory response to notify other immune cells. The aberrant release of TNF-⍺ causes rheumatoid arthritis, inflammatory bowel illness, psoriasis, psoriatic arthritis, tinnitus, and other conditions.6 Tinnitus is a condition in which a person is experiencing constant ringing in an ear in absence of an external source. The main causes of tinnitus are hearing loss, exposure to loud noise, ear wax, etc. In order to respond to injury, immune cells (microglia) produce TNF-⍺. However, if this response becomes overactive, chronic inflammatory illnesses can emerge.7 TNF-⍺ has become a therapeutic target because of its role in the development of chronic inflammatory responses. TNF inhibitors have been created and used in the treatment of inflammatory and auto-immune illnesses in clinical trials. These drugs work by interfering with TNF-⍺ signaling. Some medications work by destroying TNF-producing immune cells.8 Apart from drug therapy, other methods are used in tinnitus therapy such as phytotherapy. Ginkgo biloba is one of the herbals, frequently used in the treatment of tinnitus.
Ginkgo biloba :
Ginkgo biloba was the most commonly mentioned supplement in a worldwide assessment of dietary supplements used to cure tinnitus. It includes alkanes, lipids, sterols, benzoids, carotenoids, phenylpropanoids, carbohydrates, flavonoids, and terpenoids.9 It has some side effects including diarrhoea, nausea, bleeding, chest pain, and increased urination which are also reported.10 A plant extract's efficacy is governed by its composition, which is determined by the extraction technique, the bioavailability of its active components, and the dosage. In recent years, researchers are conducting studies of various Ginkgo biloba formulations, regardless of quality or dosage, and found that there is no scientific evidence to support the efficacy of Ginkgo biloba treatment. Several studies like this are conducted without taking into account factors like the quality of the herb, the quantity required, the reason for tinnitus for which the herb was used, and so on. Even when the methods used were defective, some researchers concluded that there was no statistical proof of a successful tinnitus treatment with Gingko. Holstein discovered evidence of efficacy for Gingko biloba extract EGb 761® in randomized, placebo-controlled trials in a more realistic situation.11 In 2003, Chinese researchers discovered that Gingko biloba extract possesses antioxidant capabilities and can block TNF-induced signaling pathways.12 The pharmacokinetics of each component of Ginkgo biloba must be determined to avoid buildup during long-term use. Because tinnitus is multifaceted, it is advised that future research analyze patients individually based on the etiology of tinnitus, treatment formulations, and different doses of Ginkgo biloba.
Blocking TNF-⍺ has been shown to diminish tinnitus symptoms, indicating that neuroinflammation plays a role in the development of tinnitus.13 Microglia and pro-inflammatory cytokines are also important in the body's normal operation. TNF-α is a crucial component of a normal immune response. TNF-α can activate the immune system to regulate. Although the current study discovered that suppressing neuroinflammatory responses reduced noise-induced tinnitus, potential adverse effects must be thoroughly investigated.
- Inflammatory responses and inflammation-associated diseases in organs (nih.gov)
- [ PDF] Kuby Immunology ebook | Download and Read Online For Free (melbhattan.com) ISBN 10: 9781464189784; ISBN 13: 1464189781
- The role of TNF-alpha in chronic inflammatory conditions, intermediary metabolism, and cardiovascular risk - PubMed (nih.gov)
- The Role of Tumor Necrosis Factor Alpha (TNF-α) in Autoimmune Disease and Current TNF-α Inhibitors in Therapeutics (nih.gov)
- Could reducing brain inflammation be a way to treat tinnitus? - RNID
- TNF- alpha inhibitors - PubMed (nih.gov)
- Ginkgo biloba in the treatment of tinnitus: An updated literature review (skums.ac.ir)
- Ginkgo biloba for tinnitus - Sereda, M - 2019 | Cochrane Library
- Ginkgo biloba extract in the treatment of tinnitus: a systematic review (nih.gov)
- Ginkgo biloba Extract Inhibits Tumor Necrosis Factor-α–Induced Reactive Oxygen Species Generation, Transcription Factor Activation, and Cell Adhesion Molecule Expression in Human Aortic Endothelial Cells | Arteriosclerosis, Thrombosis, and Vascular Biology (ahajournals.org)
- Neuroinflammation mediates noise-induced synaptic imbalance and tinnitus in rodent models (nih.gov)