Biological Activities of Betulin and Betulinic Acid

Biological Activities of Betulin and Betulinic Acid Betulin is the one of the premier pure, crystalline natural product obtained from plants through extraction and sublimation of birch bark (Lowitz 1788). Betulin and betulinic acid are closely related to each other, often found together in varying amount in different plant species when extracted by different solvents . Early anti septic property of betulin and its use become famous to be used in plaster for sterilization of cuts and wound .Studies indicated that betulin carry wound healing, cholesterol lowering activity, hepato-protecteive, anti-bacterial, anti-leishmenial, anti-viral, anti-cancer activities (Wheeler1899). Due to the high mutagenecity of HIV-1 and cancers cells in order to improve the biological activity of betulin and its derivatives various strategies were applied and still going on (Csuk, 2014), here we are presenting a coverage of the betulin, betulinic acid and its derivatives with their biological activity. Study carried on lung injury showed that betulinic acid protects sepsis induced lung injury against inflammation and indicated it as a potential regulator of the inflammation. In another study the positive effect on the acute lung injury cured by betulinic acid. The septic lung injury is generally characterized by the severe oxidative stress response, in addition to available treatment new methods are required to improve further clinical outcomes (Lingaraju et al., 2015). Lingaraju and coworkers found the effect of betulinic acid using cecal ligation and puncture model on oxidative lung injury. They treated two groups of mice with different concentration of betulinic acid, further their lung and plasma samples were collected for analysis by sacrificing the mice at 18hr. of surgery. They concluded increased antioxidants level in blood that lead to reduced lung injury in mice. The role of betulinic acid induces programmed death of human red blood cells (erythroptosis) was reported, whi ch is mediated through membrane permeabilization and calcium ion load (Gao et al.2014). Afzal and his group (Afzal et al. 2014) studied on the hypothyroidism in female albino rate for 2 months by giving them standard drug propyl thio uracil (PTU) for the induction of lower level of TSH for two months. Later on the mice were treated with standard thyroxin at a dose of 10ÃŽ ¼g/kg and the test drug betulinic acid at a dose of 20ÃŽ ¼g/kg of body weight. Finally after the two months study betulinic acid treated animals showed marked improvement in the follicle integrity that showed betulinic acid has protective activity against hypothyroidism. Two groups of semi synthetic derivatives of betulin (BT01 to BT09) and betulinic acid (AB10 to AB16) were synthesized respectively which has shown antileishmanial combined-therapy with miltefosine (Sousa et al.2014). Leishmaniasis was previously treated by miltefosine, amphotericin B, pentavalent antimony compounds, pentamidine etc. but due to thei r toxicity and biological resistance new therapeutics as betulin and betulinic acid derivatives are new avenues for its treatment. Accordingly, it is important to continue the search for new effective and less toxic treatments. Effects on the cell cycle, apoptosis / necrosis events, morphology and DNA integrity with isobologram method were used for a comparative study in between miltefosine with some of the derivative synthesized during the study. The AB13 (28-(1H-imidazole-1-yl)-3,28-dioxo-lup-1,20(29)-dien-2-yl-1H-imidazole-1-carboxylate) and BT06 (3ÃŽ ²-Hydroxy-(20R)-lupan-29-oxo-28-yl-1H-imidazole-1-carboxylate) derivatives were found to be the most active, with IC50 values of 25.8  µM, and 50.8  µM respectively. Synergistic interactions were observed between these two compounds and miltefosine. Significant morphological changes were observed using AB13, while both derivatives (AB13 and BT06) produced anti-proliferative activity through cell cycle arrest at the G0/G1 phase. Neither of these derivatives induced significant apoptosis /necrosis, as indicated by phosphatidylserine externalization and DNA fragmentation assays. Not only that, neither of the derivatives induced death in macrophage cell lines. Thus, they do not present any potential risk of toxicity for the host cells. This study identified the betulin derivative BT06 and the betulinic acid derivative AB13 as promising molecules in the development of new alternative therapies for leishmaniasis, including those involving combined-therapy with miltefosine. The solubility of betulin and its derivatives has been the most significant issue in drug development from these hydrophobic molecules . To overcome this problem nano-emulsion gels of betulinic acid were formulated(Bag and Dash 2011). They tried 20 organic solvents as well aqueous alcohol mixture to synthesize renewable nano-sized 6-6-6-6-5 pentacyclic triterpenic acid . They confirmed their results of increased hydro solubility as they found nano and micrometer length fibers using atomic force microscopy as well electron microscopy. Role of betulinic acid in manipulating the significant actions and role of xenobiotic and antioxidative enzymes in cancer initiation and proliferation were studied (Kaur and Arora 2013) . They studied on the interactio ns of betulinic acid on Sprague Dawley female rats with xenobiotic metabolizing enzymes including cytochrome b5, P420, P450, NADPH cytochrome P450 reductase, and NADH cytochrome b5 reductase (mixed function oxidases ), GST, DT-diaphorase, ÃŽ ³-glutamyl transpeptidase (phase II enzymes), alone as well as in the presence of 7,12 dimethylbenzanthracene(DMBA). The reduction in glutathione content and protein content was considered in the study to get the effect of betulinic acid. They observed the lower level of mixed function oxidases those are responsible for the conversion of carcinogen to electrophile and further increase in phase II enzymes which participated in the removal of electrophiles by sulfation or conjugation under betulinic acid treatment . Also reported that betulinic acid effectively removed or neutralized the reactive species by the action of phase II enzymes and such an effect was demonstrated from the specific activities of antioxidative enzymes which were found to b e lower as compared to positive control (DMBA-treated group) and in some cases even that of untreated control. They also found a pronounced effect of betulinic acid in protecting the animals from lipid peroxidation as evident from the reduced levels of TBARS, conjugated diene, and lipid hydroperoxide formation. Inhibition of SREBP1 activity through AMPK-mTOR-SREBP signaling pathway using betulinic acid was studied (Kim et al.2013) . Insulin-resistant HepG2 cells, primary rat hepatocytes and liver tissue from high-fat fed ICR mice were used to get insight of the mechanism responsible for anti fatty liver effect . Accumulations of triglyceride are the indication of fat deposition that was analyzed by â€Å"Oil Red O staining†, which suppression was reported by betulinic acid. Calcium-calmodulin dependent protein kinase kinase (CAMKK) and AMP-activated protein kinase (AMPK) both were activated by betulinic acid while on the other hand the mammalian target of rapamycin (mTOR), pr otein levels of sterol regulatory element-binding protein 1 (SREBP1), and S6 kinase (S6K) were all reduced when hepatocytes were treated with betulinic acid for up to 24 hours. Reduced lipogenesis leading to low lipid accumulation, nuclear translocation and repressed SREBP1 target gene expression in HepG2 cells and primary hepatocytes, suppression of SREBP1 mRNA expression and activation of AMPK via phosphorylation through betulinic acid were also highlighted in the study. Overall they suggested that betulinic acid could be promising molecule effectively ameliorating intracellular lipid accumulation in liver cells preventing fatty liver diseases. Reduction in skin hyper-pigmentation using betuinic acid from Vitis amurensis root and its anti-melanogenic effect and precise mechanism underlying the anti-melanogenic activity of betulinic acid in B16F10 cells were investigated (Jin et al. (2014). Betulinic acid significantly reduced 3-isobutyl-1-methylxanthine (IBMX)-induced melanin synt hesis by inhibiting tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 expression through the modulation of their corresponding transcription factors in B16F10 cells. In addition, phosphorylation of mitogen-activated protein kinase (MAPK)/extra cellular regulated kinase (ERK) and phosphoinositide 3-kinase (PI3K) involved in the melanogenesis processes, were ameliorated by betulinic acid treatment. Specific inhibitors were used, PD98059 (for MEK/ERK) and LY294002 (for PI3K/Akt respectively) to confirm the role of MEK/ERK and PI3K/Akt signaling pathway in the melanogenesis. Consequently, betulinic acid inhibited melanin production by tyrosinase, TRP-1, and TRP-2 inhibition through the regulation of CREB and MITF, which was accompanied with MEK/ERK and PI3K/Akt inactivation in IBMX-stimulated B16F10 cells. Finally these results expressed a novel molecular function of betulinic acid melanogenesis, which in turn enhances our understanding on the application of cosmetic therapy for reducing. Investigation were done on betulinic acid mediated fat mobilization by enhancing the level of lipolysis in adipose tissue that showed the antiobesity properties of betulinic acid with their possible mechanisms (Kim et al.2012). The lipolytic effects of betulinic acid were assayed in rat adipose tissues with inhibition of anti-lipase function and pancreatic lipase activity of betulinic acid in vitro which lead to prevent the elevation of plasma triacylglycerol levels, after oral administration of a lipid emulsion to rats where activity of cAMP-dependent phosphodiesterase was also measured. Betulinic acid inhibited pancreatic lipase activity in a dose-dependent manner at concentrations of 1.5-100à ¢Ã¢â€š ¬Ã¢â‚¬ °Ã‚ µM (ICà ¢Ã¢â‚¬Å¡Ã¢â‚¬ ¦Ãƒ ¢Ã¢â‚¬Å¡Ã¢â€š ¬ value of 21.10à ¢Ã¢â€š ¬Ã¢â‚¬ °Ã‚ µM) prevented the elevation of plasma triacylglycerol level after 2 hours of oral administration of the lipid emulsion at a dose of 100à ¢Ã¢â€š ¬Ã¢â‚¬ °mg/kg concluded the strong lipo lytic effect of betulinic acid which was mediated by cAMP-dependent phosphodiesterase inhibition. Betulinic acid exerted antiobesity effects by directly inhibiting pancreatic lipase, that can prevent the absorption of lipid from the small intestine. Recent studies on the chemical as well biological synthesis of the betulinic acid derivatives , they used fungi in combination with plant tissue culture of carrot and found that the most active derivative as , 3-(2,4-dinitrophenyl)hydrazono-lup-(20R)-29-oxolupan-28-oic acid, showed IC50values between 1.76 and 2.51ÃŽ ¼M against five human cancer cell lines (Baratto et al. 2013). The most selective, 3-hydroxy-20-(2, 4-dinitrophenyl) hydrazono-29-norlupan-28-oic acid, was five to seven times more selective for cancer cells when compared to fibroblasts. The cell cycle studies and apoptosis induction, with high cytotoxicity and selectivity on the tumour cell shown the efficacy of the transformed molecule. The design and synthesis of seco deri vtives from the alteration in the â€Å"A† ring of betulinic acid were carried (Hsin-Yi Hung 2014). A group of compounds were synthesized and their enhanced chemopreventive ability in vitro short term induced assays were done in Raji cells, C28 modified analogs shown significant activation. One of the modified derivative was found to shown 100% inhibition of EBV-EA at 1Ãâ€"103molratio/TPA ,73.4%, 35.9%, and 8.4% inhibition at 5Ãâ€"102, 1Ãâ€"102, and10molratio/TPA, respectively, comparable with curcumin at high concentration. In an investigation the role of betulinic acid co-regulation with vitamin D3,was reported that showed that betulinic acid improves insulin secretion with increasing glycogen content and glucose uptake in muscle tissue(Castro et al.2014). It was also reported that betulinic acid enhances the GLUT4 immunocontent and its translocation was supported by GLUT4 itself as well it does not cause hyper-calcemia that is very significant from the drug discovery pe rspective. In search of safe and natural treatment of obesity betulinic acid was tried as anti-obese drug on swiss albino male mice fed with high fat diet. Betulinic acid was extracted from ethanolic root extract of Clusia nemorosa (Rao et al. 2009).They treated mice at 50mg/kg body weight with control where they found significant control on the The therapeutic potential of betulinic acid on bone metastases and skeletal complications in breast cancer patients were investigated (Park et al.2014). They suggested the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. This is the first report indicating effect of betulinic acid on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-ÃŽ ². An increase in the receptor activator of nuclear factor-kappa B ligand (RANKL) / osteoprotegerin ratio was blocked by betulinic acid through down regulating RANKL protein expression in PTHrP-treated human osteoblastic cells. Not only that the inhibition of RANKL-induced osteoclastogenesis in murine bone marrow macrophages an d decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts was observed by betulinic acid. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. A pioneer study on athymic nude mice, bearing MCF-7 breast adenocarcinoma xenografts was taken as in vitro cytotoxic and in vivo anti-tumor model (Damle et al. 2013). The antitumour activity of betulinic acid was studied at 50 and100 mg/kg body weights, whereas cytotoxic activity of MCF- 7 cells with IC50 value of 13.5 µg/ml was studied by MTT assay. Betulinic acid treatment shown significant reduction in tumour size of 77 and 52% tumour size (100 and 50 mg/kg body weight respectively) in addition decreased angiogenesis, proliferation and invasion in betulinic acid treated mice were also highlighted through histopathological studies. Through topomer CoMFA , some 35 derivatives of betulinic acid were prepared and tested against HT29 human colon cancer cells (Ding et al.2013) . The contour maps showed that bulky and electron-donating groups would be favorable for activity at the C-28 position, and a moderately bulky and electron-withdrawing group near the C-3 position would improve this activity. Few of the betulin derivativeswere designed and synthesized as per the modeling result, while groups such as maleyl, phthalyl, and hexahydrophthalyl (bulky electronegative groups) were directly introduced at the C-28 position. They also found consistency with predicted and actual IC50 value of the given analogsagainst HT29 cells, proving that the present topomer CoMFA model is successful and that it could potentially forward the synthesis of newbetulinic acidderivativeswith high anti-cancer activity. Five tumour cell lines were tested against three newly synthesized derivatives where 28-O-hexahydrophthalyl betulin shown the greatest anti-cancer activities and its ICà ¢Ã¢â‚¬Å¡Ã¢â‚¬ ¦Ãƒ ¢Ã¢â‚¬Å¡Ã¢â€š ¬ values were lower than other tumour cell line except DU145.In an investigation Prunella vulgaris was used for betulinic acid and ursolic acid extraction those were responsible for the anti-estrogenic effects, suggested their potential application against estrogen-dependent tumors (Kim et al. 2014).In this study Prunella vulgaris constituents were isolated and tested their individual anti-estrogenic effects. Betulinic acids, ursolic acid, Rosmarinic acid, caffeic acid, oleanolic acid, hyperoside, rutin, were isolated from the flower stalks of P. vulgaris var. lilacina Nakai (Labiatae) which showed anti-estrogenic effects as a decreased level in the mRNA of GREB1,revealed significant anti-estrogenic effects of betulinic acid and ursolic acid, on estrogen receptors .They also demonstrated the

Factors Which Affect Decision Implementation Essay

Correct decisions, the two previous papers elaborately developed, can be arrived at only if the requisite process of ponderously putting many influencing factors in perspective is observed. Since errors in decision-making can end up being costly both for the company and its stakeholders alike, it has been seen that the use of critical thinking has proven to be essential in guiding decision makers in choosing the best options that will generate best results. But if one were to think that arriving at a logical and well-thought out decision ends the entire process of decision-making, one definitely takes the dangerous path of frustrating the process all together. A correct decision, one may argue, only proves to be beneficial to a company or organization when its implementation would translate the rigors of critical analyses into tangible results. Langdon, if only to mention, argues along the same line of thought. He maintains, â€Å"Decision makers will never leave the point of the decision without thinking about the steps necessary to implement the decision successfully† (Langdon, 2001, p. 15). Ethical Implications and Other Factors Affecting Implementation of Decision The previous discussion was able to zero in on the viable options that may gleaned from the map drawn to help BAE Systems establish greater presence in the island of Kava. It may be wise to be reminded of the decisions that were suggested hitherto: first, the company needs not only to â€Å"sustain its existing accounts, but also to set up new client-accounts done through aggressive advertisement and in-shore sales campaign† so as to ensure that the â€Å"sale of its products is commensurate with its desired expansion rate†; second, it needs to see through the â€Å"creation of an efficient and result-generating human workforce†; and third, it also is imperative that it should â€Å"create a larger warehouse, if not an adjacent processing plant in the island, so as to meet the demands of the market† It is noteworthy to mention that there are certain risks attached to the cited options. The purpose why the last paper identified them is to further inform the decision maker of the resulting benefits and costs that must be anticipated in the event of making the decision. However, to outline the varying factors that may affect th e implementation of any decision – which, if only to mention, concerns greatly the company and its stakeholders – is another area that must also be carefully looked at. Surely, the three above-cited options will generate ebbs of impact for the company in general. Two major factors can determine the success of the implementation of the suggested paths: the internal coherence of the decision itself, and the external receptivity of the stakeholders involved. The first factor pertains to the logic from which any decision is drawn; and this has already constituted a large portion of the previous studies. Every decision, if only to repeat, is arrived at after a ponderous circumscription of the problems at hand, and the generous gathering of facilitative facts to throw light into one’s judgment. If the problems were well stated, chances are, the solutions are going to be suited. The next factor is however different. This time, one has to consider other areas that affect the success rate of the decision. Roozen, De Pelsmacker and Bostyn have identified some of them: â€Å"the influence of stakeholders, organizational commitment, personal values, goals of the organization and socio demographic characteristics of individuals†, among others (2001, p. 87). In the light of the three suggested decision paths for BAE Systems, what Roozen (and company) points are certainly of paramount importance. For instance, since the company’s goal to establish a greater presence in Kava is heavily dependent on the expansion of its new sales accounts, the decision to equally expand the workforce and to create newer intra-island processing plants must be leveled against the impact such will have on the stakeholders – e. g. , will the company owners allow for an increased budget allocation to defray the expansion cost? , will the company managers be willing to oversee difficult but potential market areas within the island? , will the commitment of the newly hired sales representative be aggressive enough to meet expectations? , or will the vision of the company itself be willing to risk so much for a return of investment which will come later on? It is very important to note that BAE Systems’ vision is intricately knitted with the amount of available resources the company has, or is willing to risk for investment purposes. One way or another, the welfare of both the company and its stakeholders is the friction force that shall determine how fast or slow the implementation of the decisions pertinent to BAE Systems’ expansion in Kava island would be. Key to the company’s success in Kava is also anchored on the ethical implications the decisions have on its stakeholders. In order to clarify the moral basis for sticking into a decision, Rodgers and Gago has sought to identify many differing ethical motives in a study they conducted. They suggest that there are at least six â€Å"pathways† that justify, and thus serve a basis for a particular decision to be pursued: â€Å"psychological egoism, deontology, relativist, utilitarian, virtue ethics, and ethics of care philosophy† (Rodgers & Gago, 2001, pp. 358-359). Without having to go through their respective details, it may be good to note that the suggested options for BAE Systems are largely motivated by the â€Å"utilitarian† pathway. What does this mean? This means that the company which seeks to expand a venture must be seen primarily in terms of its ability to survive the risk. Thus, in a utilitarian approach, the company is more defined by a ‘consequentialist’ attitude in decision-making policies, in that it tries to see to it that any decision would generate the â€Å"greatest good (for) the greatest number of people† (Rodgers & Gago, 2001, p. 359). Conclusion One may properly recall that, in the Business Scenario, Alex once quipped that economics is what drives the company to further expand its presence in an island of Kava. In many ways, what he said was correct, if not telling. The overarching reason why one needs to surmount the seemingly impossible difficulties, by identifying all the contributing factors relative to the company’s vision, is indeed driven by economics. But having economics alone as the moving force behind the desired expansion of a certain company may not capture the entire picture. Any decision driven by economics therefore, one must remember, must also be tempered by the opportunities it creates for the involved stakeholders, and the ethical implications it generates seen from their perspective. Critical thinking, as always, can always help ensure that these seemingly non-economic aspects of doing business are given their due importance.

The Appeal of Fsot Essay Topics

The Appeal of Fsot Essay Topics It's important to understand that essay topics are just basic ideas that leave you pondering a notion that might be a huge deal to another person. The topics could include the following subject locations. You can also pick an emotional topic. Deciding on an emotional topic is also a superb idea. The previous section is the one which most men and women consider to be the toughest. The subjects are a breeze to comprehend, and have fully-explained example questions to ensure you master the material. You cannot reply to topics within this forum. If a number of the sample topics aren't subjects you recognize about, think about doing some research within these topics so as to eesay a broader viewpoint. Opportunity cost may be considered the 2nd best selection for using a resource. Schools should not have a thing to do with ads. Identity theft is an enormous issue for elderly men and women. 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Pest Analysis of Cambodia - 22548 Words

The Development Research Forum in Cambodia Scoping Study: Research Capacities of Cambodia’s Universities Team Members: KWOK Kian-Woon, CHAN Sopheap, HENG Chinda, KIM Sedara, NETH Baromey and THON Vimealea Research Assistants: Kelvin CHIA, CHHOENG Sotheavan and NHEM Sochea Scoping Study: Research Capacities of Cambodia’s Universities* Special Report Team Members: KWOK Kian-Woon, CHAN Sopheap, HENG Chinda, KIM Sedara, NETH Baromey and THON Vimealea Research Assistants: Kelvin CHIA, CHHOENG Sotheavan and NHEM Sochea The Development Research Forum in Cambodia Phnom Penh, August 2010 * This Scoping Study is commissioned by the Development Research Forum in Cambodia (DRF), which is a partnership of leading Cambodian research†¦show more content†¦We are also grateful to all informants and interviewees for sharing their knowledge concerning speciï ¬ c universities and their reï ¬â€šections on the higher educational landscape in Cambodia. We are responsible for errors of fact or interpretation and will make the necessary corrections in subsequent versions of this draft report. We welcome criticisms and suggestions for improving the ï ¬ nal version of the report. Study Team Team Members KWOK Kian Woon PhD (University of California at Berkeley) Associate Professor, Head, Division of Sociology Associate Chair (Academic) School of Humanities Social Sciences, Nanyang Technological University CHAN Sopheap Deputy Secretary-General Supreme National Economic Council (SNEC), Royal Government of Cambodia HENG Chinda University Liaison Manager The Learning Instit ute KIM Sedara Senior Researcher PhD Candidate Cambodia Development Resource Institute NETH Baromey PhD (University of Kassel) Head of Tourism Department Royal University of Phnom Penh THON Vimealea Research Associate (Democratic Governance and Public Sector Reform) Cambodia Development Resource Institute Research Assistants Kelvin CHIA MSc Sociology candidate, London School of Economics and Political Science BA Hons Sociology, Nanyang Technological University CHHOENG Sotheavan Community Based Natural Resource Management LearningShow MoreRelatedPest Analysis of Textile Industry1235 Words   |  5 PagesPEST ANALYSIS A PEST (Political, Economic, Social and Technological) analysis is a major part of the environmental scanning section of strategic management and it is used by companies during market research and strategic analysis. 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