Betula utilis plant- The plant belongs to the family Betulaceae. Betula utilis D. Don (Betulaceae) is a moderate- sized tree that grows up to 20 m in height. 

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... plant belongs to the family Betulaceae. In uttarakhand Betula utilis grows along moraines around Bhojbasa, close to the snout of the [3] Gangotri glacier in India . Betula utilis D. Don (Betulaceae) is a moderate-sized tree that grows up to 20 m in height ( Fig 1 ). The bark is shining, reddish-white or white, with white horizontals smooth, lenticels. The outer bark consists of layers, exfoliating in broad horizontal rolls ( Fig 2 ). The leaves are ovate-acuminate, elliptic, and irregularly serrate. The flowers bloom in May June, in pendulous spikes. The flowers are monoecious (individual flowers are either male or female, but both sexes can be found on the same plant) and are pollinated by wind. Seeds are thin and winged. The plant prefers light (sandy), medium (loamy) and heavy (clay) soils, requires well-drained soil and can grow in heavy clay soil. The plant prefers acid, neutral and basic (alkaline) soils. It can grow in semi-shade (light woodland) or no shade. It requires moist soil . Its therapeutic constitute antiseptic, aromatic, carminative and contraceptive effects. The bark contains betulin, lupeol, oleanolic acid, acetyloheanolic acid, betulitc acid, lupenone sitosterol, methyle betulonate, methyl betultriterpenoid, karachic acid. Betula utilis contains betulin up to 12% of its weight. It has [21,1] aromatic and has antiseptic properties . The bark of Himalayan birch was used centuries ago in India as paper for writing lengthy scriptures and texts in Sanskrit and other scripts . The Sanskrit word for the tree is bhûrja —sharing a similarity with other Indo European words that provide the origin for the common name “birch”. The bark is widely used for packaging material, roof construction etc. The leaves of the plant show efficacy in treatment of urinary tract infections and in kidney and bladder stones. The wood is used for construction, and the foliage for fodder. The most widespread use is for firewood, which has caused large areas of habitat to be eliminated or reduced. Parts of the plant, including the fungal growth ( bhurja-granthi ) have also long been used in local traditional medicine. Betula utilis contains betulin that can be easily converted into betulinic acid (3â-hydroxy-lup- 20(29)-en-28-oic acid) ( Fig 3 ). Studies revealed that betulinic acid inhibits growth of malignant melanoma and cancers of the liver and the lung [23] . Betulinic acid was identified as a highly selective growth inhibitor of human melanoma, neuroectodermal and malignant tumor cells and was reported to induce apoptosis in these cells. Anticancer agents with different modes of action have been reported to trigger apoptosis in [6] chemoselective cells . Alterations of mitochondrial functions such as permeability transition (PT) have been found to play a major role in the apoptosis process including cell death [13] induced by chemotherapeutic agents . The antitumor cytotoxicity of betulinic acid has been extensively studied in a panel of cancer cell lines, primary tumor samples and xenograft mouse models ( Table 1 ). Some reports suggested that betulinic acid is selectively cytotoxic against [19] melanoma cell lines . Selzer et al studied the effect of betulinic acid alone and in combination with irradiation in human melanoma cells. Betulinic acid strongly and consistently suppressed the growth and colony forming ability of all human melanoma cell lines. In combination with ionizing radiation, the effect of betulinic acid on growth inhibition was additive in colony-forming assays. Betulinic acid also induced apoptosis in human melanoma [22] cell . Zuco et al studied the in vitro cytotoxicity of betulinic acid in melanoma and non-melanoma tumor cell lines and compared with that of doxorubicin (also an anticancer drug). It was also tested on cell lines expressing a different p53 status. Betulinic acid proved active in vitro against a panel of neoplastic cell lines, including melanomas, small and non small cell lung carcinomas, ovarian and cervical carcinomas. It exerted its antiproliferative activity on all the tested lines in a very narrow range of doses (1.5- [27] 4.5 mg/ml) . Fulda et al identified betulinic acid as a new cytotoxic agent against neuroectodermal tumor cell including neuroblastoma, medulloblastoma, glioblastoma and Ewing’s sarcoma cells, which represent the most common solid tumors of childhood. Neuroblastoma cells resistant to CD95 or doxorubicin-triggered apoptosis remained sensitive to treatment with betulinic acid, and betulinic acid exhibited potent antitumor activity on primary tumor cell cultures from all neuroblastoma, all medulloblastoma with an ED50 of 3-15 mg/ml and most glioblastoma patients with an ED50 of 5-16 μg/ml ex vivo . These findings suggest that betulinic acid may be a promising new lead in the treatment of [8, 9, 10, 11] neuroectodermal tumors in vivo . Kim et al modified the C-20 alkene functional group of betulinic acid (Fig 4(a)) . The chemical modification at this position was initiated by converting the double bond to a ketone (15a) using a OsO4/NaIO4 system. The ketone functionality was readily transformed to oximes (15b and 15c). The compounds were evaluated for their cytotoxicity against the human colon carcinoma cell line HCY-116, and human melanoma cell lines M14-MEL, SK-MEL-2, and UACC-257. The results showed that when the double bond was oxidized to a ketone (15a), loss of cytotoxicity was observed, suggesting that the presence of highly electronegative oxygen atom may change the electrostatic property of betulinic acid, rendering it less toxic. Converting to oximes (15b and 15c) also appeared to result in the loss of cytotoxicity, probably due to the same reason described above. These results suggest that the cytotoxicity profile of betulinic acid derivatives may be sensitive to both the size of substituent at the C-20 position and its electrostatic properties [12] . Betulinic acid is a novel anticancer drug and induces apoptosis and hence differs from “classical” anticancer agents such as doxorubicin [8] . Betulinic acid is a prototype cytotoxic agent that triggers apoptosis by a direct effect on [10] mitochondria . In isolated mitochondria betulinic acid directly induces a loss of transmembrane potential independent of a benzyloxycarbonyl-Val-Ala- Asp-fluoromethylketone inhibitable caspase. This is inhibited by bongkrekic acid, an agent that stabilizes the PTPC (Permeability transition pore complex). Mitochondria undergo betulinic acid induced PT mediated cleavage of caspase-8 and caspase-3 in a cell-free system. Soluble factors such as cytochrome C or AIF (apoptosis-inducing factor) released from betulinic acid treated mitochondria are sufficient for cleavage of caspases and nuclear fragmentation. Addition of cytochrome C to cytosolic extracts results in the cleavage of caspase-3, but not of caspase-8. However, supernatants of mitochondria, which have undergone PT, as well as partially purified AIF, activate both caspase-8 and caspase-3 in cytosolic extracts and suffice to activate recombinant caspase-8. These finding show that the induction of mitochondrial PT alone insufficient to trigger the full apoptosis program and that betulinic acid may induce apoptosis via a [26] direct effect on mitochondria ( Fig 4(b) ). Betulinic acid has been shown to inhibit HIV [7] (Human Immunodeficiency Virus)-1replication . Based on its chemical structure, betulinic acid derivatives have been reported as inhibitors of [16] [25] HIV-1entry , HIV-protease . Since a number of betulinic acid derivatives have been shown to inhibit HIV-1 at a very early stage of the viral life cycle, these compounds have the potential to become useful additions to current anti-HIV therapy, which relies primarily on combination of reverse transcriptase and protease inhibitors. Betulinic acid extracted from the bark of Betula utilis has antibacterial activity against some important human pathogenic bacteria like Citrobacter sp., Escherichia coli , ...