Title analgesic, antimicrobial, antiviral, anticancer, anti-hyperglycemic, anti-nociceptive, hepatoprotective,

Title Therapeutic Role of Maslinic acid improve quality of health: A short reviewNaqash Goswami 1, Bin Feng, Lun Hua, Yong Zhou, Xie Peng, De WuAnimal nutrition institute, Sichuan agricultural university, Chengdu 611130, chinaRunning/short title Maslinic Acid: A review of therapeutic activities of maslinic acid.

AbstractObject. To grasp the fragmented information available on the maslinic acid, traditional uses, pharmacology of maslinic acid to explore its therapeutic potential and future research opportunities. Material and Methods.

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 All the available information on maslinic acid was collected via electronic search (using PubMed, Google Scholar, and science direct) search using keyword maslinic acid search. Results. Traditional uses of maslinic acid are recorded throughout the world where it has been used to treat various disorders. The plant materials and isolated components have shown a wide spectrum of in vitro and in vivo pharmacological activities like antidiabetic, antioxidant, and anti-inflammatory, analgesic, antimicrobial, antiviral, anticancer, anti-hyperglycemic, anti-nociceptive, hepatoprotective, and cardioprotective activities.

Conclusions. Maslinic acid arisen as a good source of traditional medicine for the treatment of various complaints. The outcomes of phytochemical and pharmacological studies reported in this review will further expand its existing therapeutic potential and provide a convincing support to its future clinical use in modern medicine.Keywords Maslinic acid, pentacyclic triterpenes, antioxidant.IntroductionIn the past years, the maslinic acid has attracted much attention as natural triterpenoids, also known as 2?,3?-dihydroxy-Olean-12-en-28-oic acid, Was first isolated in 1927 from the leaves of Crataegus oxyacantha L. and was named categoric acid ADDIN EN.

CITE <EndNote><Cite><RecNum>165</RecNum><DisplayText>1</DisplayText><record><rec-number>165</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1521716833″>165</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors></contributors><titles><title>&lt;Bioavailability and metabolism of maslinic acid, a natural pentacyclic triterpene.pdf&gt;</title></titles><dates></dates><urls></urls></record></Cite></EndNote>1 ADDIN EN.CITE <EndNote><Cite><Author>Dong</Author><Year>2017</Year><RecNum>158</RecNum><DisplayText>2</DisplayText><record><rec-number>158</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1521634912″>158</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Dong, Xiaoli</author><author>Zhang, Jiaxiao</author><author>Zhou, Zhilin</author><author>Ye, Zhennan</author><author>Chen, Jiahao</author><author>Yuan, Jifan</author><author>Cao, Fengjun</author><author>Wang, Xuanbin</author><author>Liu, Wenchao</author><author>Yu, Wenxuan</author></authors></contributors><titles><title>Maslinic acid promotes autophagy by disrupting the interaction between Bcl2 and Beclin1 in rat pheochromocytoma PC12 cells</title><secondary-title>Oncotarget</secondary-title></titles><periodical><full-title>Oncotarget</full-title></periodical><pages>74527</pages><volume>8</volume><number>43</number><dates><year>2017</year></dates><urls></urls></record></Cite></EndNote>2. More than 20,000 natural triterpenoids are known, some of which exists in free form and some in combination with another constitute, Most of them are present in plants such as seaweed, and some other parts of wax-like a coating of numerous fruits and medicinal herbs. Maslinic acid (MA) is an olean type pentacyclic triterpenoid that is similar to oleanolic acid pentacyclic triterpenoids. It possesses activity against type 2 diabetic ADDIN EN.

CITE <EndNote><Cite><Author>Zhu</Author><Year>2001</Year><RecNum>89</RecNum><DisplayText>3</DisplayText><record><rec-number>89</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”0″>89</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Zhu, Yongming</author><author>Shen, Jingkang</author><author>Wang, Huikang</author><author>Cosentino, L Mark</author><author>Lee, Kuohsiung</author></authors></contributors><titles><title>Synthesis and anti-HIV activity of oleanolic acid derivatives</title><secondary-title>Bioorganic &amp; Medicinal Chemistry Letters</secondary-title></titles><periodical><full-title>Bioorganic &amp; Medicinal Chemistry Letters</full-title></periodical><pages>3115-3118</pages><volume>11</volume><number>24</number><dates><year>2001</year></dates><urls></urls></record></Cite></EndNote>3. Maslinic acid is a common component in the diet in which olive oil and olive fruit are included ADDIN EN.CITE <EndNote><Cite><Author>Fernández-Navarro</Author><Year>2010</Year><RecNum>161</RecNum><DisplayText>4</DisplayText><record><rec-number>161</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1521685256″>161</key></foreign-keys><ref-type name=”Book Section”>5</ref-type><contributors><authors><author>Fernández-Navarro, Mónica</author><author>Peragón, Juan</author><author>Esteban, Francisco J.</author><author>Amores, Victoria</author><author>de la Higuera, Manuel</author><author>Lupiáñez, José A.</author></authors><secondary-authors><author>Watson, Ronald Ross</author></secondary-authors></contributors><titles><title>Chapter 157 – Maslinic Acid: A Component of Olive Oil on Growth and Protein-turnover Rates A2 – Preedy, Victor R</title><secondary-title>Olives and Olive Oil in Health and Disease Prevention</secondary-title></titles><pages>1415-1421</pages><dates><year>2010</year></dates><pub-location>San Diego</pub-location><publisher>Academic Press</publisher><isbn>978-0-12-374420-3</isbn><urls><related-urls><url>https://www.sciencedirect.

com/science/article/pii/B9780123744203001571</url></related-urls></urls><electronic-resource-num>https://doi.org/10.1016/B978-0-12-374420-3.00157-1</electronic-resource-num></record></Cite></EndNote>4.

While today some developed countries used plants based vegetable-rich diet research utilized them as a medicinal source to eliminate the risk of disease ADDIN EN.CITE <EndNote><Cite><Author>Setzer</Author><Year>2003</Year><RecNum>162</RecNum><DisplayText>5</DisplayText><record><rec-number>162</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1521687795″>162</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>W. N. Setzer</author><author>M.

C. Setzer</author></authors></contributors><titles><title>Plant-Derived Triterpenoids as Potential Antineoplastic Agents</title><secondary-title>Mini-Reviews in Medicinal Chemistry</secondary-title></titles><periodical><full-title>Mini-Reviews in Medicinal Chemistry</full-title></periodical><pages>540-556</pages><volume>3</volume><number>6</number><keywords><keyword>triterpenoids</keyword><keyword>cytotoxic</keyword><keyword>antineoplastic</keyword><keyword>cancer</keyword></keywords><dates><year>2003</year></dates><isbn>1389-5575/1875-5607</isbn><urls><related-urls><url>http://www.eurekaselect.com/node/80964/article</url></related-urls></urls><electronic-resource-num>http://dx.doi.

org/10.2174/1389557033487854</electronic-resource-num></record></Cite></EndNote>5. The contribution of plant drove natural pentacyclic triterpene widely acknowledge cancer therapy ADDIN EN.CITE <EndNote><Cite><Author>Thakor</Author><Year>2017</Year><RecNum>163</RecNum><DisplayText>6</DisplayText><record><rec-number>163</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1521700366″>163</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Thakor, P.</author><author>Song, W.

</author><author>Subramanian, R. B.</author><author>Thakkar, V. R.

</author><author>Vesey, D. A.</author><author>Gobe, G. C.

</author></authors></contributors><auth-address>Centre for Kidney Disease Research, School of Medicine, Translational Research Institute, The University of Queensland, Brisbane, Queensland, Australia; Department of General Surgery, Affiliated Hospital to Xuzhou Medical University, Xuzhou, China; B. R. D. School of Biosciences, Sardar Patel University, Vallabhvidyanagar, Gujarat, India; Department of Renal Medicine, The University of Queensland at Princess Alexandra Hospital, Brisbane, Queensland, Australia.</auth-address><titles><title>Maslinic Acid Inhibits Proliferation of Renal Cell Carcinoma Cell Lines and Suppresses Angiogenesis of Endothelial Cells</title><secondary-title>J Kidney Cancer VHL</secondary-title></titles><periodical><full-title>J Kidney Cancer VHL</full-title></periodical><pages>16-24</pages><volume>4</volume><number>1</number><keywords><keyword>angiogenesis</keyword><keyword>maslinic acid</keyword><keyword>proliferating cell nuclear antigen</keyword><keyword>renal cell carcinoma</keyword><keyword>vascular endothelial growth factor</keyword></keywords><dates><year>2017</year></dates><isbn>2203-5826 (Print) 2203-5826 (Linking)</isbn><accession-num>28405545</accession-num><urls><related-urls><url>https://www.

ncbi.nlm.nih.gov/pubmed/28405545</url></related-urls></urls><custom2>PMC5364332</custom2><electronic-resource-num>10.15586/jkcvhl.2017.

64</electronic-resource-num></record></Cite></EndNote>6. However maslinic acid may have utility in other pathological processes for its antioxidant and anti-inflammatory properties ADDIN EN.CITE <EndNote><Cite><Author>Huang</Author><Year>2011</Year><RecNum>67</RecNum><DisplayText>7</DisplayText><record><rec-number>67</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1521684529″>67</key><key app=”ENWeb” db-id=””>0</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Huang, Longfei</author><author>Guan, Teng</author><author>Qian, Yisong</author><author>Huang, Menghao</author><author>Tang, Xuzhen</author><author>Li, Yunman</author><author>Sun, Hongbin</author></authors></contributors><titles><title>Anti-inflammatory effects of maslinic acid, a natural triterpene, in cultured cortical astrocytes via suppression of nuclear factor-kappa B</title><secondary-title>European Journal of Pharmacology</secondary-title></titles><periodical><full-title>European Journal of Pharmacology</full-title></periodical><pages>169-174</pages><volume>672</volume><number>1</number><dates><year>2011</year></dates><urls></urls></record></Cite></EndNote>7. Furthermore, (MA) has attracted much interest due to proven its pharmacological active ingredients safety and its many biological activities against, such as antiviral, antidiabetic, as well as more recently some of the researchers focus on its anti-cancer effect on different types of cancers cells like melanoma, liver cancer, astrocytoma and colon cancer, among others, however, the mechanism of action of this compound still elusive further research required to know the mechanism of this compound for future used 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 ADDIN EN.

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Nonetheless, the antinociceptive activity of maslinic acid not reported before first time Nieto, F.R., et al., reported that (MA) have antiallodynic and analgesic property on a different type of experimental model of several types of pain 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DATA 9. This evidence indicated that maslinic acid is a multi-targeted compound to exert diverse pharmacological and therapeutic potency with many potential targeted proteins and signaling pathways this mini-review discussed in detail importance of this valuable compound against antidiabetic, anti-inflammatory, hepatoprotective, and anti-cancer lowering agent.A systematic study was carried out through a computer search of data on PubMed, ScienceDirect, and Google Scholar from published articles using keyword “maslinic acid” with the highest number of studies/research observed among triterpenes there was maslinic acid which might be associated with its pharmacological activates in different in vivo and in vitro models.Sources of maslinic acidMaslinic acid has been reported to be present in diverse species of the plant kingdom.

Maslinic acid found in edible natural sources such as fruits and vegetables such as table olives, legumes, chickpeas, eggplant, aromatic herbs, spinach, lentils, kiwi, pomegranate and mandarin 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ADDIN EN.CITE.DATA 1, 10-12. The first time maslinic acid was detected from Crataegus oxyacantha L.

, this triterpene growing interested because of health-enhancing activity. The list of the selected plant which has been reported to possess maslinic acid amount presented in (Table 1).Physio-chemical properties of maslinic acidThe IUPACE name of maslinic acid (4aS,6aR,6aS,6bR,8aR,10R,11R,12aR,14bS)-10,11-dihydroxy-2,2,6a,6b,9,9,12a-heptamethyl-1,3,4,5,6,6a,7,8,8a,10,11,12,13,14b-tetradecahydropicene-4a-carboxylic acid. Its molecular formula is C30 H48 O4 and formula weight of this compound is 472.

7 g/mole. (Reference required) Chemically, MA is a made of 30 carbon atoms grouped in five cycles that, as a substitute, have seven methyl groups, two hydroxyl groups and one carboxyl group.Role of maslinic acid in different diseases Maslinic acid has applied a variety of products in the form of beverage food, concentrated and powder. Some of its applications applied under in vitro and in vivo.

These include its beneficial activity against different diseases are discussed in the following sections.Role of maslinic acid in anticancer activityCancer is major public health problem over the worldwide high incidence of mortality occur due to cancer, it is clear now that cancer not a simple disease involving a single gene, but a complex disease involving interaction between multiple genes, either within the same cells or with those of neighboring tissue. The prevention or progression of human cancer depends on the integrity of a complex network of defense mechanism in which 300-500 genes have gone wrong, leading up-regulation of undesired products such as anti-apoptotic proteins or down-regulation of the tumor-suppressing protein ADDIN EN.

CITE <EndNote><Cite><Author>Yadav</Author><Year>2010</Year><RecNum>170</RecNum><DisplayText>13</DisplayText><record><rec-number>170</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1522140663″>170</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Yadav, Vivek R</author><author>Prasad, Sahdeo</author><author>Sung, Bokyung</author><author>Kannappan, Ramaswamy</author><author>Aggarwal, Bharat B</author></authors></contributors><titles><title>Targeting Inflammatory Pathways by Triterpenoids for Prevention and Treatment of Cancer</title><secondary-title>Toxins</secondary-title></titles><periodical><full-title>Toxins</full-title></periodical><pages>2428-2466</pages><volume>2</volume><number>10</number><dates><year>2010</year></dates><urls></urls></record></Cite></EndNote>13. The antitumor activity of the maslinic acid has become remarkable in recent few years, as evidenced by the higher number of research articles addressed this issue compared those to other biological effects. The vast majority of researcher correspond to in vitro experiments that show the antiproliferative and proapoptotic effect of maslinic acid, together with a credible mechanism of action that involves different signaling pathways ADDIN EN.CITE <EndNote><Cite><Author>Lozanomena</Author><Year>2014</Year><RecNum>131</RecNum><DisplayText>10</DisplayText><record><rec-number>131</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1515228416″>131</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Lozanomena, Gloria</author><author>Sanchezgonzalez, Marta</author><author>Juan, M</author><author>Planas, Joana M</author></authors></contributors><titles><title>Maslinic Acid, a Natural Phytoalexin-Type Triterpene from Olives — A Promising Nutraceutical?</title><secondary-title>Molecules</secondary-title></titles><periodical><full-title>Molecules</full-title></periodical><pages>11538-11559</pages><volume>19</volume><number>8</number><dates><year>2014</year></dates><urls></urls></record></Cite></EndNote>10. A compressive study conducted first time by Alam et.

,al showed the development of the field based 3D-QSAR model based on human breast cancer cell line Mcf7 in vitro anticancer activity, which defines the molecular level understanding and region of structure-activity relationship for triterpene maslinic acid and its analogs ADDIN EN.CITE <EndNote><Cite><Author>Alam</Author><Year>2017</Year><RecNum>171</RecNum><DisplayText>14</DisplayText><record><rec-number>171</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1522221957″>171</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Alam, Sarfaraz</author><author>Khan, Feroz</author></authors></contributors><titles><title>3D-QSAR studies on Maslinic acid analogs for Anticancer activity against Breast Cancer cell line MCF-7</title><secondary-title>Scientific Reports</secondary-title></titles><periodical><full-title>Scientific Reports</full-title></periodical><pages>6019</pages><volume>7</volume><dates><year>2017</year><pub-dates><date>07/20 02/27/received 06/08/accepted</date></pub-dates></dates><pub-location>London</pub-location><publisher>Nature Publishing Group UK</publisher><isbn>2045-2322</isbn><accession-num>PMC5519539</accession-num><urls><related-urls><url>http://www.ncbi.nlm.nih.

gov/pmc/articles/PMC5519539/</url></related-urls></urls><electronic-resource-num>10.1038/s41598-017-06131-0</electronic-resource-num><remote-database-name>PMC</remote-database-name></record></Cite></EndNote>14. The study conducted by Yu, Y., et al., investigated weather MA enhanced the antitumor activity with gemcitabine (GEM) (first line drug in the treatment of GBC) used MA alone and the combination of GEM on human gallbladder cancer in vivo and in vitro and its underline mechanism ADDIN EN.CITE <EndNote><Cite><Author>Yu</Author><Year>2015</Year><RecNum>172</RecNum><DisplayText>15</DisplayText><record><rec-number>172</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1522226729″>172</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Yu, Yong</author><author>Wang, Jinghan</author><author>Xia, Nianxin</author><author>Li, Bin</author><author>Jiang, Xiaoqing</author></authors></contributors><titles><title>Maslinic acid potentiates the antitumor activities of gemcitabine in vitro and in vivo by inhibiting NF-?B-mediated survival signaling pathways in human gallbladder cancer cells</title><secondary-title>Oncology Reports</secondary-title></titles><periodical><full-title>Oncology Reports</full-title></periodical><pages>1683-1690</pages><volume>33</volume><number>4</number><dates><year>2015</year></dates><urls></urls></record></Cite></EndNote>15.

In summary, there is strong evidence that maslinic acid targets a variety of signaling pathways that finally trigger an anticarcinogenic effect, both in vitro and in vivo. Consequently, maslinic acid is emerging as a potential agent for the treatment of cancer disorders, either alone or in combination with other drugs.Several studies were carried out to compare the anticancer efficacy of MA with known anti-cancer mediators. A comparative study by Dong et al.

showed that MA proved to induce cell autophagy by disrupting the combination of Bcl2 and Becilin1 in rat PC12 cells suggesting a unique molecular cancer therapy ADDIN EN.CITE <EndNote><Cite><Author>Dong</Author><Year>2017</Year><RecNum>158</RecNum><DisplayText>2</DisplayText><record><rec-number>158</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1521634912″>158</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Dong, Xiaoli</author><author>Zhang, Jiaxiao</author><author>Zhou, Zhilin</author><author>Ye, Zhennan</author><author>Chen, Jiahao</author><author>Yuan, Jifan</author><author>Cao, Fengjun</author><author>Wang, Xuanbin</author><author>Liu, Wenchao</author><author>Yu, Wenxuan</author></authors></contributors><titles><title>Maslinic acid promotes autophagy by disrupting the interaction between Bcl2 and Beclin1 in rat pheochromocytoma PC12 cells</title><secondary-title>Oncotarget</secondary-title></titles><periodical><full-title>Oncotarget</full-title></periodical><pages>74527</pages><volume>8</volume><number>43</number><dates><year>2017</year></dates><urls></urls></record></Cite></EndNote>2.Maslinic acid and diabetic The outcome of maslinic acid on glucose digestion has additionally been essentially discussed by Wen et.,al. ADDIN EN.

CITE <EndNote><Cite><Author>Wen</Author><Year>2005</Year><RecNum>173</RecNum><DisplayText>16</DisplayText><record><rec-number>173</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1522831719″>173</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Wen, Xiaoan</author><author>Sun, Hongbin</author><author>Liu, Jun</author><author>Wu, Guanzhong</author><author>Zhang, Luyong</author><author>Wu, Xiaoming</author><author>Ni, Peizhou</author></authors></contributors><titles><title>Pentacyclic Triterpenes. Part 1. The First Examples of Naturally Occurring Pentacyclic Triterpenes as a New Class of Inhibitors of Glycogen Phosphorylases</title><secondary-title>Bioorganic &amp; Medicinal Chemistry Letters</secondary-title></titles><periodical><full-title>Bioorganic &amp; Medicinal Chemistry Letters</full-title></periodical><pages>4944-4948</pages><volume>15</volume><number>22</number><dates><year>2005</year></dates><urls></urls></record></Cite></EndNote>16, a diabetic is a chronic disorder characterized by the high level of blood sugar either because of pancreatic production insulin is insufficient or because cells do not respond appropriately insulin resistance over time morbidity and mortality is a significant cause of type 2 diabetic ADDIN EN.CITE <EndNote><Cite><Author>Liu</Author><Year>2010</Year><RecNum>174</RecNum><DisplayText>17</DisplayText><record><rec-number>174</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1523434604″>174</key></foreign-keys><ref-type name=”Book Section”>5</ref-type><contributors><authors><author>Liu, Jun</author><author>Rajendram, Rajkumar</author><author>Zhang, Luyong</author></authors><secondary-authors><author>Watson, Ronald Ross</author></secondary-authors></contributors><titles><title>Chapter 158 – Effects of Oleanolic Acid and Maslinic Acid on Glucose and Lipid Metabolism: Implications for the Beneficial Effects of Olive Oil on Health A2 – Preedy, Victor R</title><secondary-title>Olives and Olive Oil in Health and Disease Prevention</secondary-title></titles><pages>1423-1429</pages><dates><year>2010</year></dates><pub-location>San Diego</pub-location><publisher>Academic Press</publisher><isbn>978-0-12-374420-3</isbn><urls><related-urls><url>https://www.sciencedirect.

com/science/article/pii/B9780123744203001583</url></related-urls></urls><electronic-resource-num>https://doi.org/10.1016/B978-0-12-374420-3.00158-3</electronic-resource-num></record></Cite></EndNote>17. A study by Liu et al.

, reported that maslinic acid exhibited significant hypoinsulinemic and glucose lowering effect in KK-Ay mice ADDIN EN.CITE <EndNote><Cite><Author>Liu</Author><Year>2007</Year><RecNum>175</RecNum><DisplayText>18</DisplayText><record><rec-number>175</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1523438754″>175</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Liu, Jun</author><author>Sun, Hongbin</author><author>Duan, Weigang</author><author>Mu, Dongyan</author><author>Zhang, Luyong</author></authors></contributors><titles><title>Maslinic acid reduces blood glucose in KK-Ay mice</title><secondary-title>Biological &amp; Pharmaceutical Bulletin</secondary-title></titles><periodical><full-title>Biological &amp; Pharmaceutical Bulletin</full-title></periodical><pages>2075-2078</pages><volume>30</volume><number>11</number><dates><year>2007</year></dates><urls></urls></record></Cite></EndNote>18. Maslinic acid and liver protection Hepatoprotective effect of MA at various doses study conducted by S. Yan et al., against alcohol-induced acute hepatotoxicity mouse model showed that application of maslinic acid pretreatment significantly suppressed nuclear factor kappa B (NF-?B), mitogen-activating protein kinase (MAPK) pathways in the liver, it is well known that alcohol stimulates the activation of these pathways ADDIN EN.CITE <EndNote><Cite><Author>Yan</Author><Year>2014</Year><RecNum>122</RecNum><DisplayText>19</DisplayText><record><rec-number>122</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1502097423″>122</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Yan, Shenglei</author><author>Yang, Huiting</author><author>Lee, Hsianglin</author><author>Yin, Meichin</author></authors></contributors><titles><title>Protective effects of maslinic acid against alcohol-induced acute liver injury in mice</title><secondary-title>Food and Chemical Toxicology</secondary-title></titles><periodical><full-title>Food and Chemical Toxicology</full-title></periodical><pages>149-155</pages><volume>74</volume><dates><year>2014</year></dates><urls></urls></record></Cite></EndNote>19.

A similar report by Wang Y-y et al., showed that MA could protect mice against LPS/D-gal-induced liver injury ADDIN EN.CITE <EndNote><Cite><Author>Wang</Author><Year>2018</Year><RecNum>179</RecNum><DisplayText>20</DisplayText><record><rec-number>179</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1529915021″>179</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Wang, Yuanyuan</author><author>Diao, Baozhong</author><author>Zhong, Lihua</author><author>Lu, Baoling</author><author>Cheng, Yu</author><author>Yu, Lei</author><author>Zhu, Liying</author></authors></contributors><titles><title>Maslinic acid protects against lipopolysaccharide/D-galactosamine-induced acute liver injury in mice</title><secondary-title>Microbial Pathogenesis</secondary-title></titles><periodical><full-title>Microbial Pathogenesis</full-title></periodical><dates><year>2018</year></dates><urls></urls></record></Cite></EndNote>20. Liver is crucial organ assume a noteworthy part in digestion and discharge of xenobiotics from the body ADDIN EN.CITE <EndNote><Cite><Author>Rane</Author><RecNum>178</RecNum><DisplayText>21</DisplayText><record><rec-number>178</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1529822076″>178</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Rane, Jesika</author><author>Jadhao, Rajesh</author><author>Bakal, RL</author></authors></contributors><titles><title>Liver diseases and herbal drugs:-A review</title></titles><dates></dates><urls></urls></record></Cite></EndNote>21.

Liver ailments are one of the leading cause of death in the world ADDIN EN.CITE <EndNote><Cite><Author>Wang</Author><Year>2014</Year><RecNum>176</RecNum><DisplayText>22, 23</DisplayText><record><rec-number>176</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1529650316″>176</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Wang, Fusheng</author><author>Fan, Jiangao</author><author>Zhang, Zheng</author><author>Gao, Bin</author><author>Wang, H</author></authors></contributors><titles><title>The global burden of liver disease: The major impact of China</title><secondary-title>Hepatology</secondary-title></titles><periodical><full-title>Hepatology</full-title></periodical><pages>2099-2108</pages><volume>60</volume><number>6</number><dates><year>2014</year></dates><urls></urls></record></Cite><Cite><Author>Blachier</Author><Year>2013</Year><RecNum>177</RecNum><record><rec-number>177</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”1529650451″>177</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Blachier, Martin</author><author>Leleu, Henri</author><author>Peckradosavljevic, M</author><author>Valla, D</author><author>Roudotthoraval, F</author></authors></contributors><titles><title>The burden of liver disease in Europe. A review of available epidemiological data</title><secondary-title>Journal of Hepatology</secondary-title></titles><periodical><full-title>Journal of Hepatology</full-title></periodical><pages>593-608</pages><volume>58</volume><number>3</number><dates><year>2013</year></dates><urls></urls></record></Cite></EndNote>22, 23.

Taken together these compelling evidence suggest that the therapeutic usefulness of maslinic acid for the hepatoprotective condition is attractive and warrants further investigation. Maslinic acid and inflammation Maslinic acid has been extensively studied for its anti-inflammatory effects under in vitro and in vivo experimental models of animals. The anti-inflammatory effect of maslinic acid was first evaluated by N.Banno et al.

, in a model of 12-O-tetradecanoyl phorbol acetate- (TPA) induced inflammation ear edema in mice ADDIN EN.CITE <EndNote><Cite><Author>Banno</Author><Year>2005</Year><RecNum>73</RecNum><DisplayText>24</DisplayText><record><rec-number>73</rec-number><foreign-keys><key app=”EN” db-id=”rdzd9z52az2wepeea9dpf9r9w20ftzxdrpxv” timestamp=”0″>73</key></foreign-keys><ref-type name=”Journal Article”>17</ref-type><contributors><authors><author>Banno, Norihiro</author><author>Akihisa, Toshihiro</author><author>Tokuda, Harukuni</author><author>Yasukawa, Ken</author><author>Taguchi, Yosuke</author><author>Akazawa, Hiroyuki</author><author>Ukiya, Motohiko</author><author>Kimura, Yumiko</author><author>Suzuki, Takashi</author><author>Nishino, Hoyoku</author></authors></contributors><titles><title>Anti-inflammatory and antitumor-promoting effects of the triterpene acids from the leaves of Eriobotrya japonica</title><secondary-title>Biological &amp; Pharmaceutical Bulletin</secondary-title></titles><periodical><full-title>Biological &amp; Pharmaceutical Bulletin</full-title></periodical><pages>1995-1999</pages><volume>28</volume><number>10</number><dates><year>2005</year></dates><urls></urls></record></Cite></EndNote>24. The anti-inflammatory effects of pentacyclic triterpenoids are largely ascribed to their ability to inhibit molecular targets such as 5-lipooxygenase (LOX), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX), and nuclear factor-kappa B (NF-?B) activities.Conclusion This review paper provides information of maslinic acid natural triterpenes with the potential to decrease the risk of diseases such as cancer, diabetic, acute and chronic liver damage, or be used as an adjuvant with different types of disease treatments for patients who already have acute or chronic damages.

It is documented that medicinal herbs such as maslinic acid have rich anticancer, anti-inflammatory, anti-diabetic, cardioprotective, anti-parasitic, anti-aging, anti-bacterial, potential, and on the forefront whenever we talk about, Natural products discovered from medicinal plants have played an important role in the treatment of different ailments. They have exhibited activity in different animal models. By generating awareness regarding usage of herbs and exploring natural product properties, healthcare professionals can play significant clinical roles as knowledge resources for masses. From information from this review, healthcare professionals can initiate discussion with colleagues to determine whether the patient may benefit from taking a specific herb or natural product. Selected plants have been explored for biological activity and further investigations into the anticancer activity of the plants showing promising activity must be undertaken.

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R., et al., Antiallodynic and analgesic effects of maslinic acid, a pentacyclic triterpenoid from Olea europaea. J Nat Prod, 2013. 76(4): p. 737-40.

10.Lozanomena, G., et al., Maslinic Acid, a Natural Phytoalexin-Type Triterpene from Olives — A Promising Nutraceutical? Molecules, 2014. 19(8): p. 11538-11559.11.Yin, M.-C., et al., Bioavailability, Distribution, and Antioxidative Effects of Selected Triterpenes in Mice. Journal of Agricultural and Food Chemistry, 2012. 60(31): p. 7697-7701.12.Lozano-Mena, G., et al., Determination of Maslinic Acid, a Pentacyclic Triterpene from Olives, in Rat Plasma by High-Performance Liquid Chromatography. Journal of Agricultural and Food Chemistry, 2012. 60(41): p. 10220-10225.13.Yadav, V.R., et al., Targeting Inflammatory Pathways by Triterpenoids for Prevention and Treatment of Cancer. Toxins, 2010. 2(10): p. 2428-2466.14.Alam, S. and F. Khan, 3D-QSAR studies on Maslinic acid analogs for Anticancer activity against Breast Cancer cell line MCF-7. Scientific Reports, 2017. 7: p. 6019.15.Yu, Y., et al., Maslinic acid potentiates the antitumor activities of gemcitabine in vitro and in vivo by inhibiting NF-?B-mediated survival signaling pathways in human gallbladder cancer cells. Oncology Reports, 2015. 33(4): p. 1683-1690.16.Wen, X., et al., Pentacyclic Triterpenes. Part 1. The First Examples of Naturally Occurring Pentacyclic Triterpenes as a New Class of Inhibitors of Glycogen Phosphorylases. Bioorganic & Medicinal Chemistry Letters, 2005. 15(22): p. 4944-4948.17.Liu, J., R. Rajendram, and L. Zhang, Chapter 158 – Effects of Oleanolic Acid and Maslinic Acid on Glucose and Lipid Metabolism: Implications for the Beneficial Effects of Olive Oil on Health A2 – Preedy, Victor R, in Olives and Olive Oil in Health and Disease Prevention, R.R. Watson, Editor. 2010, Academic Press: San Diego. p. 1423-1429.18.Liu, J., et al., Maslinic acid reduces blood glucose in KK-Ay mice. Biological & Pharmaceutical Bulletin, 2007. 30(11): p. 2075-2078.19.Yan, S., et al., Protective effects of maslinic acid against alcohol-induced acute liver injury in mice. Food and Chemical Toxicology, 2014. 74: p. 149-155.20.Wang, Y., et al., Maslinic acid protects against lipopolysaccharide/D-galactosamine-induced acute liver injury in mice. Microbial Pathogenesis, 2018.21.Rane, J., R. Jadhao, and R. Bakal, Liver diseases and herbal drugs:-A review.22.Wang, F., et al., The global burden of liver disease: The major impact of China. Hepatology, 2014. 60(6): p. 2099-2108.23.Blachier, M., et al., The burden of liver disease in Europe. A review of available epidemiological data. Journal of Hepatology, 2013. 58(3): p. 593-608.24.Banno, N., et al., Anti-inflammatory and antitumor-promoting effects of the triterpene acids from the leaves of Eriobotrya japonica. Biological & Pharmaceutical Bulletin, 2005. 28(10): p. 1995-1999.914400306070000Figure 1a: The distribution of publications on maslinic acid with respect to document type1058545806450001962150428625No of publications 00No of publications Figure 1a: Year-wise distribution of publications on maslinic acid for the last ten years.Maslinic acid Country All fieldsUsa 10China 84Japan 13Germany 13South Korea 5India 10France 7Spain 68Taiwan 8Brazil 4Total 222.Table 2:Top 10 country results research of Maslinic Acid research based on PubMed online search. Date: 5/13/201874930026225500PubMed search mortality related liver diseaseSerial no Common name Botnical name Amout mg/kg dry weight Refrencess1 Pomegranate Punica granatum 10.8 2 Kiwi Actinidia deliciosa 3 Lentils Lens culinaris 4 Spinach Spinacia oleracea 1260 5 Legume Fabaceae 6 Olive Olea europaea 7 Chickpea Cicer arietinum 61.8 8 Eggplant Solanum melongena 840 9 Mango Mangifera indica 10 Indian Jubie 11 12 Effect Genes ReferencesAnticancer Antidiabetic Inflammation Antibacterial Cardio protective Antifungal Antioxidant Analgesic

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