Antimicrobial and anti-inflammatory activity of Mitragyna speciosa L. extracts

According to the World Health Organization (WHO), more than 80% of the world's population relies on traditional medicine and phytotherapy for primary healthcare needs. Medicinal plants, also called medicinal herbs, have been investigated and used in ethnomedicine practices since prehistoric times. Several modern studies indicate that primary and secondary metabolites concentrated in plant phytocomplexes have remarkable pharmacological activity. The composition of phytocomplexes is ranging from peptides, carbohydrates, unsaturated fatty acids, aldehydes, alkaloids, essential oils, and polyphenols. In some cases, have been exploited against human and animal pathogens, including bacteria, fungi and viruses.

Mitragyna speciosa, known as “Biak” or “Kratom”, has been used in traditional popular medicine for centuries in many southeast Asian countries, especially Thailand and Malaysia.

Mitragyna leaves extract is well known for the antinociceptive, antitussive, stimulant, and analgesic effect, while their antioxidant, antimicrobial and anti-inflammatory properties are so far underexploited.

Antibacterial activity of M. speciosa leaves extracts was investigated by disk diffusion method. The surprising inhibition zone around extract-impregnated paper disk placed into bacterial inoculated agar plates at low minimum inhibitory concentrations (MICs), prompted further studies. Antimicrobial screening assay of M. speciosa extracts shows, in different methanolic alkaloid extracts, relatively wide inhibition zones against the test strains compared with the positive control.1

The antibacterial activity was confirmed against Salmonella typhi and Bacillus subtilis. The inhibition zones of M. speciosa (methanolic extract) (29–30 mm) and concentrated alkaloids (30–33 mm) were greater than the positive control with Chloramphenicol (23–24 mm), a relatively broad-spectrum antibiotic. The minimum inhibitory concentration (MIC) was assessed for both methanolic extract and purified alkaloids mixture. With the tested bacterial strains, the MIC were 6.25 mg/mL and 3.25 mg/mL respectively.

The anti-inflammatory effect of M. speciosa methanolic extract was investigated by Shaik Mossadeq et al. with different tests, aiming to recognize it from the antinociceptive activity.2

1 S. Parthasarathy, J. Bin Azizi, S. Ramanathan, S. Ismail, S. Sasidhara, Mohd I. M. Said, S. Mahsufi Mansor. Evaluation of Antioxidant and Antibacterial Activities of Aqueous, Methanolic and Alkaloid Extracts from Mitragyna Speciosa (Rubiaceae Family) Leaves. Molecules 2009, 14(10), 3964-3974.

2 W.M. Shaik Mossadeq, M.R. Sulaiman, T.A. Tengku Mohamad, H.S. Chiong, Z.A. Zakaria, M.L. Jabit, M.T.H. Baharuldin, D.A. Israf. Anti-Inflammatory and Antinociceptive Effects of Mitragyna speciosa Korth Methanolic Extract. Medicine Principle and Practice 2009, 18, 378–384.

It was demonstrated that M. speciosa extract (100 and 200 mg/kg, i.p.) could strongly inhibit the mice’s writhing response in the acetic acid induced abdominal constriction test. The mechanism of action might involve a peripheral pathway mediated by lipoxygenases inhibition of and/or cyclo-oxygenase activity.

A limit of this model was the overlapping effect of other drugs, requiring a more selective evaluation. It was however stated that the extract contained bioactive compounds acting both centrally and peripherally, therefore M. speciosa extract possesses both antinociceptive and anti-inflammatory activities.

Very interesting are the results of the Carrageenan-induced rat paw edema test, a conventional method used to evaluate the acute phase of the anti-inflammatory effect of drugs and natural products. Inflammation induced by carrageenan is acute, nonimmune and highly reproducible, characterized by cardinal signs of inflammation like edema, hyperalgesia, and erythema, which develop rapidly after subcutaneous injection.

These effects result from action of proinflammatory agents like bradykinin, histamine, complement and reactive oxygen. Such agents can be generated in situ at the site of insult or by infiltrating cells, for example neutrophils that readily migrate to the inflammation site. Anti-inflammatory activity of pretreatments with acetylsalicylic acid (ASA) and M. speciosa extract, were compared. Pretreatment with ASA exhibited a significant inhibitory action on paw edema at 1 and 3 h after carrageenan injection, decreasing edema by 44 and 60%, respectively. Nevertheless, the group treated with M. speciosa extract (200 mg/kg) showed the best activity, reducing edema by 60 and 63%, respectively, 4 and 5 h after carrageenan injection, even when the inhibitory effects of the other treatments progressively declined. M. speciosa extract (100 and 200 mg/kg) inhibited the development of paw edema more than ASA, demonstrating maximum inhibition during the first 3 h after challenge. These results suggest that M. speciosa extract may suppress the early phase of edema, possibly by inhibiting the synthesis, release, or actions of the various hyperalgesic mediators which are known to mediate acute inflammation.

Finally, another test was carried out to gain further insight into chronic anti-inflammatory effects. Results bring researchers to associate the extract activity with the inhibition of the synthesis of many mediators involved in the formation of fibrovascular tissue, including chemokines, cytokines and eicosanoids. In conclusion the anti-inflammatory activity of M. speciosa may result from a combination of inhibition of pro-inflammatory mediator release and vascular permeability in addition to enhanced immunity, stimulation of tissue repair and healing processes