Credit: Frontiers in Pharmacology (2024). DOI: 10.3389/fphar.2024.1484040

Within Tibetan medicine, the medicinal herb Terminalia chebula (T. chebula) is well-known for its extensive therapeutic properties. Its usefulness against bacteria, viruses, oxidation, inflammation, glycemia, and tumors has been elucidated in classic texts as well as in modern research, and it is prescribed for numerous physical conditions.

However, whether T. chebula might serve as a safe, effective treatment for mild cognitive impairment (MCI) has not been sufficiently studied. As an early step, a research team has conducted a comprehensive review of related literature from 1990–2024 to evaluate the herb’s potential for further research in this area.

The team includes researchers from the College of Pharmacy and Meishan Hospital; the School of Ethnic Medicine; and the Research Institute of Integrated Traditional Chinese Medicine and Western Medicine, all within the University of Traditional Chinese Medicine in Chengdu, China.

Their work appears in Frontiers in Pharmacology.

Mild cognitive impairment is considered a median stage between signs of normal aging and dementia. Left untreated, it can progress to Alzheimer’s disease, the most common cause of dementia. The review notes, “Moreover, residing in high-altitude, low-oxygen environments, such as Tibet, can induce cognitive dysfunction and structural brain changes, especially above 4,000 m.”

According to the Alzheimer’s Association website, Alzheimer’s disease was the fifth-most common cause of death of people aged 65+ in the U.S. as of 2021. Approximately 7 million people in the US currently live with Alzheimer’s, and this figure is projected to rise to nearly 13 million by 2050.

The geographical distribution and botanical morphology of T. chebula. (A) The geographical distribution of T. chebula in the world. (B) The leaf of T. chebula. (C) The fruit of T. chebula. (D) Specimen diagram of T. chebula leaves. (E) Specimen diagram of T. chebula fruit. The above pictures were all accessed through GBIF.org (https://www.gbif.org/) on 2023-05-22. Credit: Frontiers in Pharmacology (2024). DOI: 10.3389/fphar.2024.1484040

How Tibetan medicine informs this review

Traditional Tibetan medicine, evolved and practiced over thousands of years, categorizes MCI as a form of amnesia, part of so-called Jie Xie Syndrome, “attributed to disturbances in ‘Long,’ [generally the basis of circulation, energy, and thoughts] including a weak heart, excessive worry, and anxiety,” according to the review.

“Tibetan medicine addresses age-related diseases by preventing aging and tonifying Yang [generally a negative, expansive biological force] to regulate ‘Long’ disorders and restore the body’s balance,” write the researchers.

T. chebula is derived from the dried fruit of a deciduous tree within the Combretaceae family, native to parts of China, India, Malaysia and Myanmar. The herb is often blended with others to provide treatment of conditions ranging from asthma and bronchitis to high cholesterol and blood pressure, from skin conditions to digestive disorders, from improving infection resistance to increasing immunity.

Molecular mechanism of MCI alleviation by T. chebula. Abbreviations: IL-6, interleukin-6; IL-1β, interleukin-1β; TNF-α, tumor necrosis factor-α; ROS, reactive oxygen species; Nrf2, nuclear factor erythroid 2-related factor 2; CAT, catalase; SOD, superoxide dismutase; GSH, Glutathione; NF-κB, nuclear transcription factor-κB; MAPK, mitogen-activated protein kinase. Credit: Frontiers in Pharmacology (2024). DOI: 10.3389/fphar.2024.1484040

Notably, studies published in 2011 and 2020 found that the likelihood of depression is higher in patients with MCI than in those with normal cognitive function. Additionally, research published in 2021 established that a T. chebula ethanol extract yielded anti-depressant-like and anxiolytic-like effects in mice, and reduced levels of monoamine oxidase (MAO-A), an enzyme associated with a number of psychiatric disorders, including Alzheimer’s disease, depression, and attention deficit hyperactivity disorder.

On this basis, this new review assesses T. chebula’s chemical profile of 171 components—including flavonoids, phenolic acids, tannins, triterpenoids, volatile compounds, and others—and considers their possible use in MCI treatment. The researchers believe that T. chebula’s anti-inflammatory, antioxidant, antiviral and hypoglycemic effects will mostly serve to mitigate MCI symptoms.

They write, “The neuroprotective effects of T. chebula originate from its potent anti-inflammatory and antioxidant properties. It shields neurons from oxidative stress and neurotoxicity, reduces neuronal inflammation, and supports synaptic plasticity while enhancing cerebral blood flow. Moreover, T. chebula appears beneficial for sleep, a critical issue in MCI, although additional research is needed to fully understand its mechanisms in improving sleep quality.”

However, they caution that more work is needed to explore specific chemical components of the herb, and to delineate its quality standards.

Moreover, the researchers acknowledge numerous challenges remaining with regard to MCI treatment, owing to a lack of diagnostic standards; limited treatment methods; the absence of well-developed traditional Tibetan medicines as well as challenges in developing related drugs; no provision for individualized treatments; the need for attention to long-term condition management and treatment adherence; and inadequate psychological and social support systems.

In conclusion, the team recommends that new work should address all of these areas. The researchers end their review on a hopeful note: “As future research progresses, Tibetan medicine, T. chebula, shows immense promise in treating MCI and offers potential benefits to patients by improving the overall human quality of life.”