Alzheimer's disease is a debilitating neurodegenerative condition that gradually erodes memory, cognition, and daily functionality. Affecting over 6.9 million Americans aged 65 and older, the prevalence of Alzheimer's is expected to surge to over 153 million cases globally by 2050. Despite the availability of medications such as Donepezil and Memantine, which only provide symptomatic relief, there remains no cure or treatment that can reverse or halt the progression of the disease. However, a new study offers hope for a potential breakthrough using Mitragyna speciosa in the fight against Alzheimer’s.

What is Mitragyna speciosa?

Mitragyna speciosa, or Kratom, is a tropical plant native to Southeast Asia, renowned for its traditional uses in pain relief, cough management, and the treatment of hypertension. Part of the coffee family (Rubiaceae), Kratom has also been employed as a morphine substitute in addiction recovery practices in local cultures. Known as "Kratom" in Thailand and "Ketom" in Malaysia, the plant contains a range of bioactive compounds that exhibit pharmacological properties such as anti-inflammatory, antioxidant, antidepressant, and neuroprotective effects. These qualities have inspired researchers to investigate its potential therapeutic role in addressing Alzheimer's disease.

The research

A team of scientists from Walailak University in Thailand examined how Mitragyna speciosa could target the root causes of Alzheimer’s. The researchers utilized a combination of advanced computational techniques and laboratory experiments to explore the plant's compounds. Methods like network pharmacology and molecular docking were employed to assess potential therapeutic interactions between the plant’s bioactive compounds and Alzheimer-related proteins. In vitro experiments further validated the findings in a controlled laboratory setting.

Identifying key compounds

The study focused on 19 phytochemical compounds extracted from Mitragyna speciosa, including acetylursolic acid, beta-sitosterol, isomitraphylline, and speciophylline. These compounds were selected based on their adherence to Lipinski’s Rule of Five, ensuring drug-like properties, and underwent rigorous toxicity screening to confirm their safety for potential use in therapeutic applications.

Targeting Alzheimer’s proteins

The researchers identified 60 key proteins involved in Alzheimer’s disease as potential targets for Mitragyna speciosa compounds. These proteins are crucial in the formation of tau tangles and beta-amyloid plaques, two hallmark pathologies of Alzheimer’s. Molecular docking studies revealed that the plant's compounds demonstrated high binding affinities for proteins such as AKT1, GSK3B, NFkB1, and BACE1 - all involved in neuronal survival, inflammation, and the pathological aggregation of tau and beta-amyloid proteins.

Results of the study

1. Reduction in oxidative stress: oxidative stress, caused by an imbalance of reactive oxygen species (ROS), plays a significant role in neuronal damage in Alzheimer’s. The study showed that extracts from Mitragyna speciosa effectively reduced oxidative stress in neuronal cells exposed to hydrogen peroxide, a standard model for oxidative stress. The ethanolic (EE) extract showed the highest potency, followed by distilled water (DWE) and pressurized hot water (PHWE) extracts.

2. Improved neuroprotection in cells: researchers used SH-SY5Y neuronal cells to model oxidative stress. When pre-treated with Mitragyna speciosa extracts, the cells showed improved survival rates and a reduction in oxidative damage. The extracts not only enhanced cell viability but also decreased ROS production, indicating strong neuroprotective effects.

3. Bioactive richness: the study highlighted the plant's rich assortment of neuroprotective compounds, including alkaloids, phenolics, and flavonoids. These compounds, known for their antioxidant properties, help neutralize free radicals and protect neurons from oxidative stress. Among the extracts tested, the ethanolic extract exhibited the highest concentration of these beneficial compounds.

4. Molecular pathway discoveries: the research further uncovered the pathways through which the plant’s compounds exert their effects, such as the inhibition of tau hyperphosphorylation, reduction of beta-amyloid aggregation, and modulation of inflammatory responses. These compounds also appeared to improve glucose metabolism and reduce neuronal inflammation—both of which are disrupted in Alzheimer's disease.

5. The possibility of a holistic approach with Kratom: one of the most exciting aspects of this study is the multi-target approach of Mitragyna speciosa. Unlike conventional medications, which often target a single pathway, the compounds in Kratom interact with multiple proteins and pathways simultaneously. This holistic strategy addresses both the symptoms and the underlying causes of Alzheimer's disease, which is known to be multifactorial, involving genetic, environmental, and lifestyle factors.

A glimpse into the future

While the findings from this study are promising, further research - including clinical trials—is needed to confirm these results in humans and determine the optimal dosage and formulation for therapeutic use. The researchers caution that while the results are encouraging, Mitragyna speciosa should not be considered a standalone solution but rather a complementary approach alongside existing treatments.

Conclusion

The study conducted by researchers from Walailak University, University of Kentucky and University of Chittagong demonstrates the potential of Mitragyna speciosa as a natural, multi-target treatment for Alzheimer's disease. By reducing oxidative stress, preventing protein aggregation, and modulating inflammation, the plant’s compounds could lead to more effective therapies for the condition. The plant's natural origin and broad spectrum of activity make it a promising candidate for future drug development.

Although much more work remains to be done - especially in terms of clinical trials and regulatory approval - the study’s findings provide hope for the millions of people affected by Alzheimer's disease. Mitragyna speciosa could one day revolutionize the approach to treating this devastating condition, offering a natural, safe and effective alternative to existing treatments.