Impact of Cannabis Leaf (Sakon Nakhon Cultivar) Extracts on Anticholangiocarcinoma Activity

Sakon Nakhon, Thailand, is a key site for cultivating Squirrel Tail cannabis, which is used for medicinal, health, and nutritional purposes. This ‘Squirrel Tail cannabis’ has various potential applications. Addressing significant issues and enhancing the potential of this important local herbal plant is crucial, particularly in the Northeastern region of Thailand, including the provinces of Nakhon Phanom, Sakon Nakhon, and Khon Kaen (Sriamporn et al., 2004). This region has the highest prevalence of liver fluke (Opisthorchis viverrini) disease and cholangiocarcinoma (bile duct cancer) in the world. Cholangiocarcinoma (CCA) is a major public health concern in Thailand. CCA is currently classified as a chronic disease and ranks among the top five causes of death, with up to >10,000 people dying from this condition annually (Chaiteerakij et al., 2017, Elgenidy et al., 2022). The Northeastern region of Thailand, particularly the provinces of Sakon Nakhon and Nakhon Phanom, has the highest prevalence of liver fluke disease and CCA (Perakanya et al., 2022). Chronic inflammation leads to the production of free radicals, which can damage various biomolecules, including DNA. In particular, alterations in DNA bases are linked to the carcinogenic process. Patients often seek treatment at advanced stages of the disease (Kay et al., 2019), resulting in most patients either dying or surviving for <5 years after treatment, with only a small proportion living beyond this period. Cannabis (Cannabis sativa) originates from tropical regions, specifically the Squirrel Tail strain. It is an annual herb, and historical records suggest that cannabis has been used for over four thousand years (Simiyu et al., 2022). Compounds with psychoactive effects have been identified in cannabis, particularly in the leaves and flowers. Cannabis contains significant compounds known as cannabinoids, such as delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and cannabinol (CBN) (AL Ubeed et al., 2023). In Thailand, there are reports of cannabis being used in traditional Thai medicine formulations. In these medicinal preparations, nearly every part of the cannabis plant is utilised, including the roots, stems, leaves, and female flowers, which have the most potent effects. Traditional Thai medicinal texts describe all parts of the cannabis plant as having a bitter and intoxicating taste. The leaves are recognised for their ability to treat asthma, stimulate appetite, and enhance vitality (Bhuiya et al., 1992). However, they can also induce feelings of fear, dizziness, and hallucinations (Berridge and Tan, 1993). The flowers are noted for their properties in treating nervous disorders, inducing sleep, stimulating appetite, and alleviating phlegm in the throat, among other uses (Stasiłowicz et al., 2021). Squirrel Tail cannabis has been incorporated into traditional Thai medicine formulations and is listed in the National List of Essential Medicines of Thailand. To encourage and advance the use of cannabis-based formulations within the healthcare system, the National Drug System Development Committee has announced a list of seven herbal medicine formulations (cannabis) for use in cancer patients. Natural products have played an essential role in traditional medicine for centuries, providing a wealth of bioactive compounds with diverse biological activities. Cannabis sativa is one such plant that has garnered renewed interest in oncology research due to its wide array of biologically active constituents, including cannabinoids, terpenoids, flavonoids, and phenolic compounds. These components have demonstrated a range of therapeutic effects, such as anti-inflammatory, antioxidant, and antiproliferative activities, which are highly relevant for cancer treatment. These herbs have been tested in the laboratory for their ability to reduce cancer cell growth (Liu et al., 2010). However, detailed studies on the effects of different parts of the ‘squirrel tail cannabis Sakon Nakhon strain’ on cancer inhibition are still lacking. The current research team has conducted preliminary studies on the chemical composition and antioxidant properties of squirrel tail cannabis, revealing intriguing findings and suggesting potential for inducing cancer cell death. Since the key compounds in this formulation include highly effective antioxidants (Silva-Reis et al., 2023), international studies have reported their ability to inhibit various types of cancer (ALSalamat et al., 2024). However, there are no reports in Thailand on the use of Squirrel Tail cannabis to target mechanisms in CCA or liver cancer. Research on the utilisation of ‘Squirrel Tail cannabis’ is therefore essential. Moreover, it is crucial to study its cancer-fighting mechanisms and develop it as a health food innovation for cancer patients, since it represents a significant advancement with local potential.

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