THERAPEUTIC POTENTIAL AND FUTURE PROSPECT OF PSIDIUM GUAJAVA LINN

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The decoction of leaves was screened for hypoglycaemic activity in alloxan induced diabetic rats. In both acute and sub acute tests, the extract showed statistically significant hypoglycaemic activity. apart from these the treatment with Psidium guajava L. aqueous leaf extract (0.01-0.625 mg/ml) also showed significant inhibition on LDL glycation in a dose-dependent manner. Tannins, flavonoids, pentacyclic triterpenoids, guiajaverin, quercetin and other chemical compounds present are speculated to account for the observed hypoglycaemic and hypotensive effects of the leaf extract.

Whatever the case may be, the undisputable truth is that this subject requires further investigations. Psidium guajava is an excellent anti-LDL glycative agent whose potential therapeutic uses can been extended to the prevention of a variety of cardiovascular and neurodegenerative diseases associated with glycations. Some investigators suggested that the hypoglycaemic components of guava fruits might involve ursolic acid, oleanolic acid, arjunolic acid and glucuronic acid. the antiglycation activities of guava fruit were relevantly and directly related to its polyphenolic content (extractable polyphenols 2.62-7.79%).

CARDIOVASCULAR SYSTEM AFFECT


Psidium guajava has been reported to have action on the heart. In a study of an aqueous leaf extract, Psidium guajava L. exhibited cardioprotective effects against myocardial ischaemia-reperfusion injury in isolated rat hearts. Ojewole, (2005) showed that an aqueous leaf extract caused hypotension in the experimental animal model used via cholinergic mechanisms. the acute intravenous administrations of the leaf extract produced dose dependent, significant reductions in systemic arterial blood pressures and heart rates of hypertensive. Belemtougri et al (2006) found that an aqueous and ethanolic leaf extracts of Psidium guajava L. inhibits  intracellular calcium release.

An Aqueous leaf extract of Psidium guajava L. significantly and dose-dependently (0.25-2mg/ml) contracted theaorta rings. the sensitivity of the aortic rings to cumulative doses of Psidium guajava L. was significantly enhanced in the presence of phentolamine suggesting that the effect of Psidium guajava L.was to a large extent mediated by activation of an alpha-adrenoceptor and to a lesser extent by activating via calcium ion channels.The antihypertensive effect was also observed on the pink guava puree.

Psidium guajava Linn leaf is used traditionally in Indian medicine to control hypertension in human. the aim of this work was to study the hypotensive effect of Psidium guajava Linn. leaf extract in human. hypertension is due to the activity of the angiotensin-Converting Enzyme that catalyzes the conversion of the inactive Angiotensin I to the active Angiotensin II. Angiotensin II functions as a potent vasoconstrictor causing hypertension. Hence, ACE inhibitors are considered to be the first choice treatment of hypertension. The ACE inhibitory activity of Psidium guajava Linn. leaf extract in human was studied by its in vitro inhibitory effect on human serum-ACE using the substrate FA-PGG (N-(3-(2-Furyl) acryloyl)-Lphenylalanyl- glycyl-glycine). The enzyme kinetics of ACE inhibition was investigated by Michaelis–Menten kinetics and Lineweaver–Burk graph and Vmax and Km values were calculated. The results show that there is a decrease in both Vmax and Km values in the presence of Psidum guajava leaf extract. The decreased Vmax and Km seen with Psidium guajava indicates that Psidium guajava binds to other alternative sites rather than the active site of the ACE and hence the inhibition is uncompetitive. The decreased Vmax/Km value indicates decreased catalytic ability/affinity of enzyme-substrate due to the presence of the inhibitor Psidium guajava leaf extract. From these we could conclude that P. guajava Linn leaf extract inhibit human serum-ACE uncompetitively and it has hypotensive effects in human.

ANTIPROLIFERATIVE ACTIVITY
Anti-proliferative activity of essential oil from 17 Thai medicinal plants on human mouth epidermal carcinoma (KB) and murine leukemia (P388) cell lines using MTT assay were investigated. An amount of 1/104 cells/well of KB cell line and 1/105 cells/well of P388 cell line were treated with the oil samples at different concentrations ranging from 0.019 to 4.962 mg/ml. In KB cell line, Guava (Psidium guajava L.) leaf oil showed the highest anti-proliferative activity with the IC50 value of 0 .0379 mg/ml (4.37 times more potent than vincristine). The results demonstrated the potential of essential oil from Thai medicinal plants for cancer treatment.

Acetone extracts from guava branch (GBA) preparations were evaluated for their cytotoxic activity in HT-29 cells.As a preliminary test to confirm the cytotoxicity of GBA in HT-29 cells, the cells were pretreated with 50, 100, and 250 μg/ml GBA. HT-29 cells were originally derived from a human colon cancer and were chosen as representative hypovascular tumor. These cells had shown strong tolerance to anticancer agents in vitro and in vivo. We attempted to determine the cytotoxic activity of GBA and the cytotoxic effect of these extracts as measured by the MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5,- diphenyltetrazolium bromide) reduction assay.  GBA showed potent cytotoxic activity in HT- 29 cells. GBA effected a 30 - 70% reduction in cell viability as compared to the control, in a dose-dependent manner. In order to assess the cytotoxicity occurring in cells measured in the sub-G1 phase were approximately 30-fold greater for the GBA-treated HT-29 cells than for the control. These results clearly indicate that the anti-proliferative effect of GAE on HT-29 cells was attributable to apoptosis and suggest that guava branch may be an important natural anticancer chemotherapeutic agent.

In conclusion, it is clearly demonstrate that GBA significantly induces cytotoxicity and an increase in the sub-G1 phase of HT-29 cells. these results show that GBA may exert anticancer activity by the induction of apoptosis via inhibition of cell cycle. Therefore, our   results suggest that GBA may be a potential candidate for a novel therapeutic agent in the field of anticancer drug discovery.

FUTURE PROSPECT
Psidium guajava
L. will be a useful plant for developing newly therapeutic agent for herbal and pharmaceutical industries, since it was used traditionally in many countries with its wide therapeutic range, it shows that the  different prospectes for researches in future .areas where researches are required for asure its therapeutic effects are –
·         Anticancer activity
·         Antidiabetic activity
·         Antihypertensive activity

The cytotoxic capacity of the essential oils based on a pro-oxidant activity can make them excellent antiseptic and antimicrobial agents for personal use i.e. for purifying air, personal hygiene, or even internal use via oral consumption and insecticidal use for preservation of crops or  food stock, recent studies have demonstrated that the pro-oxidant activity of some essential oil or some of their constituents, as also that of some polyphenols is very efficient in reducing local tumor volume or tumor cell proliferation by apoptotic and or necrotic effects. We have shown that the guava leaf essential oil has cytotoxic on the human cervical cancer cell lines have shown anticancer activities on KB and P388 cell lines. Many tumor cells are characterized by severe changes in energy metabolism and mitochondrial overproduction and permanent oxidative stress.

Essential oils due to their capacity to interfere with mitochondrial function, may add pro-oxidant effect and thus become genuine antitumor agent. Many radical producing agent are in fact used in antitumor treatments. in the case of essential oiles, redical production could be very well controlled and targeted without presenting by it any toxic or mutagenic side effects to any healthy tissues. Essential oils or their active constituents could be included in vectorized liposome that would allow bettering defining the quantities applied. Thus, the Psidium guajava L. essential oil could make their way into the modern medical domain. Machenism behind the anticancer activity , of psidium guajava l. is not known. pharmacological action of  p.guajava l.  is under study. and plant found to be very good activitites against cancerous cell as shown in therapeutic potential. but more estimations or elucidations are required  .

Active factors of P. guajava fruits involve ursolic acid, oleanolic acid, arjunolic acid and glucuronic acid , saponin combined with oleandolic acid: morin- 3-O-a-L-lyxopyranoside and morin-3-O-a-Larabinopyranoside pentane-2-thiol and flavonoids: guaijavarin and quercetin. In comparison, huge amounts of b-sitosterol glucoside, brahmic acid, and polyphenolics (165.61 ± 10.39 mg⁄ g dried crude extract) including gallic acid, ferulic acid, and quercetin  and flavonoids (82.85 ± 0.22 mg⁄ g dried crude extract) , and triterpenoids  exist in guava leaves. Thus, it is clear that P. guajava contains many component sepereted to display efficacy against cancer.

Acetone extract was highly active against gram positive and fungal strains while all of the extracts were equally active against gram-negative strains.  it is concluded that acetone extract of Psidium guajava is highly active against 74.72% of the total 91 microbial strains studied. The acetone extrac of P.guajava should further be studied for its phytochemical constituents in order to elucidate the active principle within the extract which can turn out to be a novel antimicrobial agent of the future.

CONCLUSION
Therapeutic potential of P.guajava, review presented numerous evidences of its strong antidiarrhoeal, antimicrobial, antioxidant and other so many activities. P.guajava L. has received much attention in the literature over the past 10 years and a variety of potential beneficial effects have been elucidate. it is imperative that more clinical and pharmacological studies should be conducted to investigate the unexploited potential of this plant.

Many essential oil components and extract of P.guajava L. have been screened for antiproliferative agents, and showen suppressive activity when tested on number of human cancer cell lines including colon cancer, gastric cancer, human liver tumor, pulmonary tumor, breast cancer, leukemia and others. In recent study , essential  oil from the leaves of the plant was reported to exhibit anticancer  activities on KB Aand P388 cell lines. it was reported that essential oil from the leaves of P.guajava exhibited the highest antiproliferative activity towards KB cells .

A survey of the literature shows P. guajava is mainly known for its antispasmodic and antimicrobial properties in the treatment of diarrhoea and dysentery. Has also been used extensively as a hypoglycaemic agent. Many pharmacological studies have demonstrated the ability of this plant to exhibit antioxidant, hepatoprotection, anti-allergy, antimicrobial, antigenotoxic, antiplasmodial, cytotoxic, antispasmodic, cardioactive, anticough, antidiabetic, antiinflamatory and antinociceptive activities, supporting its traditional uses. Suggest a wide range of clinical applications for the treatment of infantile rotaviral enteritis, diarrhoea and diabetes. Wide range of therapeutic potential of psidium guajava linn has been reported which has many useful pharmaceutical applications.

REFERENCES
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