Ursolic Acid and Oleanolic Acid: Pentacyclic Terpenoids with Promising Anti-Inflammatory Activities

Author(s):  
Dharambir Kashyap ◽  
Ajay Sharma ◽  
Hardeep S. Tuli ◽  
Sandeep Punia ◽  
Anil K. Sharma
2020 ◽  
Vol 6 (2) ◽  
pp. 134-146 ◽  
Author(s):  
Kehkashan Arshad Qamar ◽  
Ahsana Dar Farooq ◽  
Bina S. Siddiqui ◽  
Nurul Kabir ◽  
Sabira Begum

Aims: The aim of the current study was to identify active compound(s) responsible for the antiproliferative effects of O. basilicum and explore their underlying mechanism/s. Background: Plants have been the source of medicines for the treatment of various diseases since ancient times. Ocimum basilicum (Sweet Basil, Bobai Tulsi) has been used in the folk medicine for the treatment of human liver, spleen and stomach cancers. Background: Plants have been the source of medicines for the treatment of various diseases since ancient times. Ocimum basilicum (Sweet Basil, Bobai Tulsi) has been used in the folk medicine for the treatment of human liver, spleen and stomach cancers. Objective: To emphasize the importance of O. basilicum as a potential novel non-toxic alternative to the conventional anticancer therapy. Method: O. basilicum (aerial parts) methanolic extract and fractions were screened against HT-144, MCF-7, NCI-H460 and SF-268 human cancer cell lines using sulforhodamine B assay. The more active Petroleum Ether Insoluble (PEI) fraction was fractionated into six sub-fractions (OB-1 to OB-6). Four pure compounds (3-O-methyl ursolic acid, oleanolic acid, 3-epi-ursolic acid and ursolic acid) were isolated from the more potent sub-fraction OB- 6. Triple channel immunofluorescence microscopy was employed to observe the effects of methanolic extract, PEI fraction, sub-fractions OB-5 and OB-6, 3-epi-ursolic acid and oleanolic acid on the cytoskeleton and nuclei of MCF-7 cells. Result: The methanolic extract and the PEI fraction exhibited selectively greater growth inhibition against MCF-7 cell line (TGI: 56 and 36.2 µg/ml, respectively). By using triple channel immunofluorescence microscopy, it was observed that the methanolic extract, PEI fraction, sub-fraction OB-5 and 3-epi-ursolic acid induced irregular mitotic spindle formation and slowing of mitotic progression in MCF-7 cells while sub-fraction OB-6 induced mitotic arrest in the prophase stage. F-actin aggregation was also visible in PEI fraction, subfraction OB-5 and 3-epi-ursolic acid treated MCF-7 cells. Conclusion: These results emphasize the importance of O. basilicum as a potential novel non-toxic alternative to the conventional anticancer therapy and suggest that it inhibits the growth of MCF-7 cancer cells via multiple mechanisms such as interaction with the microtubules and mitotic spindle apparatus, and F-actin aggregation.


Author(s):  
Mingzhu Luan ◽  
Huiyun Wang ◽  
Jiazhen Wang ◽  
Xiaofan Zhang ◽  
Fenglan Zhao ◽  
...  

: In vivo and in vitro studies reveal that ursolic acid (UA) is able to counteract endogenous and exogenous inflammatory stimuli, and has favorable anti-inflammatory effects. The anti-inflammatory mechanisms mainly include decreasing the release of histamine in mast cells, suppressing the activities of lipoxygenase, cyclooxygenase and phospholipase, and reducing the production of nitric oxide and reactive oxygen species, blocking the activation of signal pathway, down-regulating the expression of inflammatory factors, and inhibiting the activities of elastase and complement. These mechanisms can open up new avenues for the scientific community to develop or improve novel therapeutic approaches to tackle inflammatory diseases such as arthritis, atherosclerosis, neuroinflammation, liver diseases, kidney diseases, diabetes, dermatitis, bowel diseases, cancer. The anti-inflammatory activity, the anti-inflammatory mechanism of ursolic acid and its therapeutic applications are reviewed in this paper.


Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4957
Author(s):  
Wanda Baer-Dubowska ◽  
Maria Narożna ◽  
Violetta Krajka-Kuźniak

Naturally occurring pentacyclic triterpenoid oleanolic acid (OA) serves as a good scaffold for additional modifications to achieve synthetic derivatives. Therefore, a large number of triterpenoids have been synthetically modified in order to increase their bioactivity and their protective or therapeutic effects. Moreover, attempts were performed to conjugate synthetic triterpenoids with non-steroidal anti-inflammatory drugs (NSAIDs) or other functional groups. Among hundreds of synthesized triterpenoids, still the most promising is 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), which reached clinical trials level of investigations. The new group of synthetic triterpenoids are OA oximes. The most active among them is 3-hydroxyiminoolean-12-en-28-oic acid morpholide, which additionally improves the anti-cancer activity of standard NSAIDs. While targeting the Nrf2 and NF-κB signaling pathways is the main mechanism of synthetic OA derivatives′ anti-inflammatory and anti-cancer activity, most of these compounds exhibit multifunctional activity, and affect cross-talk within the cellular signaling network. This short review updates the earlier data and describes the new OA derivatives and their conjugates in the context of modification of signaling pathways involved in inflammation and cell survival and subsequently in cancer development.


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