A REVIEW OF MITRAGYNA PARVIFOLIA (ROXB) KORTH

 

GEOGRAPHICAL VARIATIONS AND ALKALOIDS
It has been observed that environmental factors play a vital role in modifying the content and structure of the alkaloids. There occurs a wide variation in the pattern of alkaloids present in leaves of Mitragyna parvifolia obtained from different geographical sources in South East Asia 9.

Three distinct alkaloidal sequences are found to exist:
1.      C (9)- H allo-epiallo series of closed E ring indole and oxindole alkaloids
2.      C (9)-H normal-pseudo series of closed E ring indole and oxindole alkaloids
3.      C (9)-H normal-pseudo series of open E ring indole and oxindole alkaloids

More than one sequence of alkaloids could be found in some plants and there are indications that M. parvifolia exists in different geographical variants and possibly chemical races 8.

The examination of leaves of M. parvifolia from Kekirawe, Sri Lanka, has revealed the presence of four alkaloidal N- oxides, viz Akuammigine N-oxide, Speciophylline N-oxide, Uncarine N-oxide and Dihydrocorynantheol N-oxide. The tertiary alkaloids present are Akuammigine, Tetrahydroalstonine, pteropodine, isopteropodine, speciophylline, uncarine F, dihydrocorynantheol and corynantheidol 10. The plants growing in Burma reported the presence of rhyncophylline, isorhyncophylline, hirusteine, dihydrocoryntheine and angustine 11. Also a yellow alkaloid designated Gu 5, not of Indole or Oxindole type has been isolated from Burmese leaves of M. parvifolia6. The alkaloids rhyncophylline, isorhyncophylline, pteropodine, isopteropodine and akuammigine were found to be present in the Ceylonese variety ofM. parvifolia. Also two new alkaloids not previously reported from Mitragyna species were isolated and characterized. These were found to be hirsutine (an open E ring indole alkaloid) and corynoxeine (an open E ring oxindole alkaloid) 12. The Cambodian variety was found to contain rhyncophylline and isorhyncophylline13.

The alkaloidal profile was even found to be variable in trees of Mitragyna parvifolia growing in different regions of India.

The young leaves obtained from the plants growing in the Uttar Pradesh (Lucknow) region were found to contain two different alkaloidal sequences (Fig 4, Fig 5). Thus the trees in this region have reported the presence of six oxindolic alkaloids namely Mitraphylline, isomitraphylline, pteropodine, isopteropodine, speciophylline and uncarine F3.

Trees from Kerela region reported the presence of C (9)-H normal pseudo series of open E ring alkaloids although no corresponding indole alkaloids were found. This region bears trees rich in alkaloids namely cilliaphylline, Rotundifoline, Isorotundifoline, rhyncocilline, rhyncophylline and isorhyncophylline8. Presence of Pteropodine and isopteropodine is a common feature of all the Indian leaves but are found to be missing in M. parvifolia trees obtained from Kerela state7.

Leaves of the plants obtained from Bihar and West Bengal do not contain the same alkaloids as those obtained from Kerala 13. The alkaloids reported from trees in this region were found to be both indole and oxindole derivatives, which were all closed E ring alkaloids. The oxindole alkaloids (mitraphylline, isomitraphylline, pteropodine, isopteropodine, speciophylline, uncarine F) are all isomeric, although the remaining isomers of the group (uncarines A and B) do not seem to be present.

The leaves of the plant in Maharashtra region (Fig-6) had an entirely different set of alkaloids from those of the same species collected in Kerala14.

Seasonal variations also affect the alkaloidal content of Mitragyna trees. In the genus Mitragyna the occurrence of angustine appears to be restricted. The alkaloid angustine (belonging to the category of pyridino-indolo-quinolizidinone alkaloid), was found to be maximum during the first half of the year whereas the second half of the year reported the same alkaloid in trace amounts15.

Some Interesting facts regarding alkaloids of Mitragyna parvifolia
1.      The pattern of alkaloids in M. parvifolia leaves growing in India and South East Asia shows all alkaloids obtained from Indian sources (with the exception of plant material from Kerela state) to be Closed E ring alkaloids, whereas those from Burma and Cambodia are E seco type.

2.      A second interesting point is that with the exception of alkaloids obtained from trees growing in Kerela, none of the alkaloids from Indian sources are substituted in the aromatic ring. Substituted alkaloids are found in the plant material from Burma and Cambodia. The link between the two groups appears to be in trees growing in Ceylon which produces both types of alkaloids, substituted and unsubstituted.

3.      The plant material from Kerela state bears unsubstituted indole alkaloids as the enzyme systems necessary for 9- substitution is lacking in plants of this region 8.

4.      The natural occurance of both open and closed E ring oxindoles together in various species of Mitragyna without the presence of corresponding closed E ring indole alkaloids suggests that the closed E ring oxindole alkaloids might arise by the ring closure of open E ring oxindoles.

PHARMACOLOGICAL PROFILE

Traditional Uses
Mitragyna parvifolia
is credited with several medicinal properties and has been widely used by tribal people and other ayurvedic practitioners. The traditional uses of the different parts of the plant are:-
1.Bark and roots:
The bark and roots are used to treat fever, colic, muscular pain, burning sensation, poisoning, gynecological disorders, cough, edema and as aphrodisiac. Stem bark of M. parvifolia is also used in biliousness and applied for muscular pains by the local inhabitant of Tunkur district, Karnataka, India. Bark paste with water is applied externally to relieve muscular pains while the decoction of the bark is given to cure fever by the tribals of Sonaghati of Sonbhadra district, Uttar Pradesh. Powdered bark along with fruits of Phyllanthus emblica is boiled in water and inhaled through mouth for toothache by the Kaadar tribes of Topslip, Tamil Nadu. The Valaiyans tribe, inhabitants of Sirumalai hills, Madurai district, Western Ghats, Tamil Nadu use trunk bark of M.parvifolia to get relief from rheumatic pain.

2.Fruit juice
The fruit juice augments the quantities of breast milk in lactating mothers and also works as lactodepurant.

3.Leaves:
Wounds and ulcers were dressed with its leaves to alleviate pain, swelling and for better healing[16].Fresh leaf juice of M. parvifolia is used to cure jaundice by the tribals of the Chenchus, Yerukalas, Yanadis and Sugalis of Gundur District, Andhra Pradesh17.

Recent Advances in Pharmacological activities of M.parvifolia

Acute toxicity studies
The preliminary acute toxicity studies on the leaf extracts have been carried out according to the OCED- 2001 guidelines using swiss albino mice. The methanolic extract, ethyl acetate extract and the alkaloid rich fraction prepared from the leaves were used for studying acute toxicity. The plant was found to be practically non toxic, as the LD50 dose recorded was 5g/kg/wt18.

Antinociceptive activity
The antinociceptive activity of the ethanolic extract of dried leaves of M. parvifoliahas been evaluated using the Tail-flick method in mice at various dose levels of 100, 200 and 30mg/kg p.o. The extract demonstrated marked antinociceptive activity at the highest dose of 300mg/kg as the maximal possible effect of 39.59% was found to exist. The effect was comparable to that of standard drug, Ibuprofen (43.63%). The results of this study have established the antinociceptive activity of leaf extracts of M. parvifolia 1.

Antiarthritic activity
The methanolic extract of M. parvifolialeaves has been investigated for its antiarthritic potential in rodent models of mice and rats. For evaluation of antiarthritic potential Acetic acid induced vascular permeability in mice and Freund’s adjuvant induced arthritis in rats has been used. Extract was administered at doses of 125, 250 and 500g/kg p.o. the percentage inhibition rates in paw edema in either of the models was in a dose dependent manner. The doses showed inhibition rates of 22.1%, 35.9% and 51.3% in acetic acid induced permeability model. On similar grounds inhibition rates of 36.74%, 39.94% and 59.54% was observed in Freund’s adjuvant induced arthritis in rats19.

Anticonvulsant activity
The anticonvulsant effects of ethanolic extract from the leaves of M. parvifoliaproduced by cold maceration technique was investigated by studying the effects of seizures induced by pentylenetetrazole (PTZ) and maximal electroshock (MES) convulsive methods in mice. The extracts were administered orally at doses of 100, 250 and 500mg/kg. The extract at doses 250 and 500mg/kg suppressed tonic hind limb extensions (THLE) induced by MES. An increase in the onset time and the percentage protection of tonic hind limb extensions were observed. Extract at the highest dose of 500mg/kg exhibited protector effects in PTZ-induced seizures. A delay in the onset of tonic convulsions and an increase in the percentage protection were observed20.

Anti-inflammatory activity
Studies have been conducted to evaluate anti-inflammatory activity of the ethanolic extract of dried leaves of M. parvifoliausing the Carrageenan-induced paw edema method in rats at dose levels of 100, 200 and 300mg/kg p.o. Phenylbutazone at dose level of 80mg/kg p.o. was used as the standard drug. Potent anti-inflammatory effect of the extract at dose level of 300mg/kg (37.99% inhibition) was found and this effect was equivalent to that of phenylbutazone (42.02%). The mechanism of inhibition is believed to be the inhibition of cyclooxygenase leading to inhibition of prostaglandin synthesis. The results of this study thus established the anti-inflammatory activity of leaf extract of M. parvifolia1.

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