Therapeutic potential of Polyalthia cerasoides stem bark extracts against oxidative stress and nociception

Polyalthia cerasoides [Source: Wikipedia]

   Annonaceae is an ecologically important tropical plant family of ca. 2500 species and 109 genera occurring in South East Asia, Malay archipelago, New Guinea, Pacific islands, Australia, India, Africa Madagascar, Neotropics and North America [http://annonaceae.myspecies.info/]

  Polyalthia cerasoides (Roxb.) Bedd. is a medium sized tree belonging to Annonaceae family which is widely distributed in almost all forests of Deccan India up to 3000 ft. In southern India, the plant is almost exclusively used for its edible fruits and seeds [B. C. Goudarshivananavar et al. 2015]. The stem bark of this plant is used as tonic to combat stress and pain by local medicinal practitioners and experimental studies have demonstrated its normalizing activity on brain neurotransmitters, moderate cytotoxicity and antioxidant activity in vitro. This gave an interest to investigate the pharmacological bioactivities of the Polyalthia cerasoides. Our study pictured that Ethyl acetate extract of P. cerasoides stem bark demonstrated a significant analgesic and anti‑inflammatory activity with ROS scavenging potential. This gave a strong scientific evidence for considering the P. cerasoides stem bark extracts as natural antioxidants targeting algesia and inflammation. therefore this concluded that P. cerasoides stem bark could be used as a therapeutic drug in oxidative stress induced pathological conditions.

ABSTRACT OF THE PUBLISHED ARTICLE

Background: Polyalthia cerasoides is a medicinal plant known for its ethnopharmacological importance. Despite this, investigation related to its therapeutic benefit is still

unexplored. 

Aim: To evaluate the stem bark extracts of Polyalthia cerasoides for pharmacological activities relating to inflammation, nociception and oxidative stress using in vivo

and in vitro models. 

Materials and Methods: Pet ether, ethyl acetate and chloroform fractions of the stem bark were evaluated for anti‑inflammatory activity by carrageenan‑induced hind paw edema in rats. Anti‑nociceptive activity in mice was assessed using thermally and chemically induced analgesic models. The free radical quenching potential of the extracts was initially analyzed using the in vitro DPPH photometric assay, Hydroxyl radical scavenging and Lipid Peroxidation assays. Then modulatory effect of the extracts on in vivo antioxidant system was evaluated by carbon tetrachloride induced hepatotoxicity and subsequent measurements of antioxidant enzymes such as Superoxide dismutase, Catalase and Peroxidase from the liver homogenate. 

Results: Among the tested fractions, ethyl acetate extract had substantially inhibited the inflammation by 68.5% that was induced by subcutaneous carrageenan injection whereas pet ether and chloroform extract showed only minimal inhibitory effect. Investigation of the anti‑nociceptive activity revealed that the ethyl acetate fractions had significantly repressed the algesia in both the analgesic experimental models. In vitro and in vivo individual antioxidant assays demonstrated that the ethyl acetate fraction has strong free radical quenching potential which also restores the endogenous hepatic enzymes.

Conclusion: The ethyl acetate fraction enriched with flavinoids and steroids from Polyalthia cerasoides stem bark has potent bioactivity to combat inflammation, ROS and pain. This needs further characterization for potential therapeutic applications.

KEYWORDS: Analgesia, anti‑inflamatory, carageenan, catalase, lipid peroxidation, nociception, reactive oxygen species

For further informations, kindly go the below links:

http://www.ncbi.nlm.nih.gov/pubmed/26865738

FREE TEXT ARTICLE: http://www.ancientscienceoflife.org/text.asp?2015/35/2/70/171667

Synthesis of Oxadiazole–Morpholine derivatives and manifestation of the repressed CD31 Microvessel Density (MVD) as tumoral angiogenic parameters in Dalton’s Lymphoma - By Vigneshwaran V.

V. VIGNESHWARAN,

PhD Scholar, Kuvempu University

NOTE: THIS IS A RE-POST ADOPTED FROM THE WEBPAGE OF MOLECULAR BIOMEDICINE LABORATORY (MBL). Click here to view the original article 

                         Tumor tissues recruit the blood vessels and displays an enormous vasculature. This is in fact responsible for the tumors aggressiveness and metastasis. The evidence for the involvement of neovasculature in tumor progression and metastasis has been shown in numerous studies. Hence we have attempted to repress the tumoral vasculature as an approach to inhibit the proliferation of cancer cells, by using a novel synthetic molecule. We have developed a series of novel synthetic molecule 4-[2-(5-substituted-phenoxymethyl/ propyl)-[1,3,4]-oxadiazol-2-ylsulfanyl)-ethyl]-morpholine analogs 6a–l, which is a combination of oxadiazole and morpholine in a compact system. Among the synthesized series, the research team at MBL has identified a potent neoplastic and antiangiogenic drug – 6a, which had prolonged the survival of the tumor bearing animal by repressing the CD31 Microvessel density (MVD) and tumor recurrence. With this compound, MBL has identified and developed four potent anti-angiogenic and tumor suppressor drug with the others being BP-1B (Synthetic), BP-1T (Synthetic), Lupeol (Plant derived triterpenoid) etc.

This research article is published in the journal Bioorganic Chemistry (2015) by the publisher Elsevier. The research publication is an outcome of joint collaboration comprising MBL research team and Department of Chemistry, Yuvaraja’s College, University of Mysore, Mysore. The authors of this article include, Mohammed Al-Ghorbani, V. Vigneshwaran, V. Lakshmi Ranganatha, B.T. Prabhakar, Shaukath Ara Khanum (names in the order as published in the journal). The compound synthesis and characterization were carried out by research team at Mysore. The study involving screening, cell culture (in-vitro) and in-vivo animal experimentation were done at MBL, Shimoga.

Abstract of the publication (As published in the journal- Bioorganic Chemistry):

A series of oxadiazole derivatives possessing morpholine 6a–l were synthesized by nucleophilic substitution reaction of key intermediates [1,3,4]-oxadiazole-2-thiol derivatives 5a–l with 4-(2-chloroethyl) morpholine. Compounds 6a–l were evaluated for their in vitro and in vivo antitumor potential in Dalton’s Lymphoma Ascites (DLA) tumor cells. Among 6a–l series, compound 6a with concentration ~8.5 μM have shown extensive cytotoxicity in vitro and 85% reduction in tumor volume in vivo, attributing an excellent anti-proliferative capability towards the cancer cells. Compound 6a has extensively inhibited the Microvessel Density (MVD) or tumoral neovasculature which was evident from the CD31 immuno staining and peritoneal H&E staining. The major reason for the antiproliferative activity of compound 6a was due to the repression of tumor vasculature. 

PUBMED LINK: http://www.ncbi.nlm.nih.gov/pubmed/26005956

A priceless opportunity to see Bharat Ratna C.N.R. Rao at Indian Institute of Science (IISc), Bengaluru

Eminent scientist and Bharat Ratna awardee Prof. CNR Rao and Sri Siddar

amaih, Honorable Chief Minister of Karnataka and other dignitaries standing

for the Karnataka State anthem at the inauguration of state science and tech-

nology award function organised by Vision group of science and technology

(VGST), at Indian Institute of Science (IISc), Bangalore.

              That day I have been to Bangalore, what is now called Bengaluru in true Kannada flavor, as an accompaniment to my Research Supervisor for his award ceremony along with some of my close friends. It was organized by Vision Group of Science and Technology (VGST) a research wing of Government of Karnataka, India. JN TATA auditorium where we were seated was without much fanfare with silent yet busily awaiting audience whom were mostly scientist from all over Karnataka and their family. Although most of the audiences would be highly enthusiastic and anticipating to get the awards from the hands Mr.Siddaramaih, Honorable Chief minister of Karnataka, and Bharat Ratna C.N.R. Rao, my sole expectation was to have the glimpse of an exemplary scientist and to listen to his speech. The auditorium was very cheerful when the chief scientist and dignitaries arrived. It was great and cheerful moment for me too as I am seeing them all for the very first time. Though he is well known among scientist communities all around the world, Chintamani Nagesa Ramachandra Rao, also known as C.N.R. Rao grabbed the attention of entire nation when he was awarded Bharat Ratna, the highest civilian award, from the Indian nation.  He is the first Indian to reach the h-index of 100, reflecting the enormity of the body of his published research work. But even before, I was aware of him, as one of my friend’s friend was doing Ph.D. under his guideship in Bengaluru. The person who was well known for his sharp and tiff words targeting government in support of research and development, was one that day really cool and humorous in his speech. He looked imperturbable and ever smiling, and the sentences that he ended up were not that pompous but generated high sounding claps from the audiences.

Prof. C.N.R. Rao interacting with the senior scientist at IISc, Bangalore, during the VGST award function.

  

Prof. CNR Rao interacting with Chief Minister Siddaramaih 

How a Scientist-Politician meet, generated grants.

            It is really every reformers or sufferer’s dream to question and rebuke the responsible persons for the cause. How joyous it would be for the scientist and public when CNR Rao could utilize the opportunity and create that situation thereby requesting the ministers who are his co-dignitaries on the same dais to fund the required grants for science and technology. To everyone’s surprise and to my expectations, his application was immediately answered by the Chief Minister Siddaramaih, that the government would infuse more grants in to the research and development sector. Karnataka is one of the countable and very few states in India that is pioneering research oriented activities. It is many a time made possible by this kind of scientist-politician interaction and the place where such an ambience is absent, reflects poor research performance, which is obvious and evident from the majority of Indian states. Karnataka in this aspect is truly inspiring, advantageous and pioneering. With the perfect blend of research scholars, scientists, industries, central and state research institutes, the place is really doing magic in R&D field.

Chief Minister Siddaramaih addressing the scientist 

community during the state science and technology

award function organizedby Vision Group of Science 

and Technology (VGST) at  JN Tata auditorium, IISc, 

Bengluru. 

Siddaramaih – A true Siddha!

    Please wait before getting into conclusions. You may wonder whether this article is being politicized. But honestly, the answer is No.  After all, Siddaramaih – A true Sidda, is not my statement. When CNR Rao was speaking, he warmly praised Chief Minister Siddaramaih as a true Siddha, but in the true sense it did not appeared to be panegyric or a formal speech intended as a public compliment. The term literally means an ascetic who has achieved enlightenment. True to the statement he looked calm and collected. But unfortunately I have forgotten some of the interesting conversation between CNR Rao and the Chief Minister Siddaramaih. The CM recollected many of his fun filled college days as a law student in the University of Mysore when he spoke. He too counter-praised CNR Rao for being honoured with the highest civilian award, but even his statement was also not panegyric. It appeared to the public that really have a good understanding with each other. In a brisk tone he made an enigmatic speech encompassing the current and future research developmental activities. Shri. Siddaramaih one amongst the few graduated Chief Ministers of India, was clever in making his oration which had a brilliant proportion of scientific discussion rather than taking advantage of the opportunity for the political promotion. 

MOMENTOUS MEET: Chief Minister Siddaramaih, Government of Karnataka, holding the hands and having a discussion with my research supervisor, Dr. B.T. Prabhakar, Assistant Professor, Department of Biotechnology, Kuvempu University. Bharat Ratna CNR Rao and Shri S.R. Patil, Minister for Planning and Statistics, IT, BT, Science & Technology could also been seen alongside.  

Dr. B.T. Prabhakar during the award ceremony at IISc., Bangalore, where he was awarded VGST- Young Scientist award, by Vision Group of Science and Technology (VGST), A research wing of Government of Karnataka.

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