Natural Products Chemistry and Pharmacognosy Commons^™

Development And Evaluation Of Therapeutics In The Setting Of Radiation Injury, Karin Emmons Thompson

Theses and Dissertations (ETD)

The possibility of an incident involving radiation exposure is at the forefront of public attention in the current global environment. With a greater number of entities possessing nuclear weapons and increased demand for nuclear power, the concern for uncontained exposure to radiation is increasing. In light of these developments, the need for treatments that may be easily stored and administered to large numbers of people who have been exposed to high doses of total body irradiation (TBI) is more urgent than ever before.

Our goal was to identify and develop novel, drug-like small molecules that would exhibit radiomitigating activity for …

Studies On Antidyslipidemic Effects Of Morinda Citrifolia (Noni) Fruit, Leaves And Root Extracts., Saf-Ur Rehman Mandukhail, Nauman Aziz, Anwar Gilani

Department of Biological & Biomedical Sciences

Background: The objective of present study was to provide the pharmacological basis for the medicinal use of Morinda citrifolia Linn in dyslipidemia using the aqueous-ethanolic extracts of its fruits (Mc.Cr.F), leaves (Mc.Cr.L) and roots (Mc.Cr.R). Results: Mc.Cr.F, Mc.Cr.L and Mc.Cr.R showed antidyslipidemic effects in both triton (WR-1339) and high fat diet-induced dyslipidemic rat models to variable extents. All three extracts caused reduction in total cholesterol and triglyceride levels in triton-induced dyslipidemia. In high fat diet-induced dyslipidemia all these extracts caused significant reduction in total cholesterol, triglyceride, low density lipoprotein-cholesterol (LDL-C), atherogenic index and TC/HDL ratio. Mc.Cr.R extract also caused increase …

The Marine Sponge Metabolite Mycothiazole: A Novel Prototype Mitochondrial Complex I Inhibitor., J Brian Morgan, Fakhri Mahdi, Yang Liu, Veena Coothankandaswamy, Mika B. Jekabsons, Tyler A. Johnson, Koneni V. Sashidhara, Phillip Crews, Dale G. Nagle, Yu-Dong Zhou

Natural Sciences and Mathematics | Faculty Scholarship

A natural product chemistry-based approach was applied to discover small-molecule inhibitors of hypoxia-inducible factor-1 (HIF-1). A Petrosaspongia mycofijiensis marine sponge extract yielded mycothiazole (1), a solid tumor selective compound with no known mechanism for its cell line-dependent cytotoxic activity. Compound 1 inhibited hypoxic HIF-1 signaling in tumor cells (IC(50) 1nM) that correlated with the suppression of hypoxia-stimulated tumor angiogenesis in vitro. However, 1 exhibited pronounced neurotoxicity in vitro. Mechanistic studies revealed that 1 selectively suppresses mitochondrial respiration at complex I (NADH-ubiquinone oxidoreductase). Unlike rotenone, MPP(+), annonaceous acetogenins, piericidin A, and other complex I inhibitors, mycothiazole is a mixed polyketide/peptide-derived compound …

Antispasmodic, Bronchodilator And Blood Pressure Lowering Properties Of Hypericum Oblongifolium - Possible Mechanism Of Action, Arif-Ullah Khan, Munasib Khan, Fazal Subhan, Anwar Gilani

Department of Biological & Biomedical Sciences

The crude extract of Hypericum oblongifolium (Ho.Cr), which tested positive for flavonoids, saponins and tannins caused concentration-dependent (0.1-1.0 mg/mL) relaxation of spontaneous and high K(+) (80 mM)-induced contractions in isolated rabbit jejunum preparations, suggesting a Ca(++) antagonistic effect, which was confirmed when pretreatment of the tissue with Ho.Cr produced a rightward shift in the Ca(++) concentration-response curves, like that caused by verapamil. Ho.Cr relaxed carbachol (1 mu M) and high K(+)-induced contractions in guinea pig tracheal preparations. It caused a dose-dependent (3-100 mg/kg) fall in arterial blood pressure of rats under anesthesia. In isolated guinea pig atria, Ho.Cr caused inhibition …

Discovery Of Quinic Acid Derivatives As Oral Anti-Inflammatory Agents, Kui Zeng

Theses and Dissertations (ETD)

Quinic acid (QA) esters found in hot water extracts of Uncaria tomentosa (a.k.a. Cat’s claw) exert anti-inflammatory activity through mechanisms involving inhibition of the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB). Herein, we described the synthesis and biological testing of novel QA derivatives. Inhibition of NF-κB was assessed using A549 (Type II alveolar epithelial-like) cells that stably express a secreted alkaline phosphatase (SEAP) reporter driven by an NF-κB response element. A549- NF-κB cells were stimulated with TNF-α (10 ng/mL) in the presence or absence of QA derivative for 18 hours followed by measurement of SEAP activity. Amide substitution at …

Development And Validation Of A Rapid Method For The Detection Of Latrunculol A In Plasma., Jiajiu Shaw, Frederick A. Valeriote, Joseph Media, Tyler A. Johnson, Taro Amagata, Karen Tenney, Phillip Crews

Natural Sciences and Mathematics | Faculty Scholarship

Latrunculol A is a recently discovered 6,7-dihydroxy analog of the potent actin inhibitor latrunculin A. Latrunculol A has exhibited greater cytotoxicity than latrunculin A against both murine and human colon tumor cell lines in vitro. Currently, there are no reports regarding the bioavailability of latrunculol A in vivo. This study was undertaken as a prelude to pharmacokinetic assessments and it is the first work where bioavailability of latrunculol A was studied. In the present work, a simple plasma preparation and a rapid HPLC method have been developed. Mouse plasma containing latrunculol A was first treated by acetonitrile and then centrifuged …

Antispasmodic And Vasodilator Activities Of Morinda Citrifolia Root Extract Are Mediated Through Blockade Of Voltage Dependent Calcium Channels, Anwarul Hassan Gilani, Saf-Ur-Rehman Mandukhail, Javeid Iqbal, Masoom Yasinzai, Nauman Aziz, Aslam Khan, Najeeb-Ur-Rehman

Department of Biological & Biomedical Sciences

Background: Morinda citrifolia (Noni) is an edible plant with wide range of medicinal uses. It occurs exclusively in tropical climate zone from India through Southeast Asia and Australia to Eastern Polynesia and Hawaii. The objective of this study was to explore the possible mode(s) of action for its antispasmodic, vasodilator and cardio-suppressant effects to rationalize its medicinal use in gut and cardiovascular disorders. Methods: Isolated tissue preparations such as, rabbit jejunum, rat and rabbit aorta and guinea pig atria were used to test the antispasmodic and cardiovascular relaxant effects and the possible mode of action(s) of the 70% aqueous-ethanolic extract …

Pharmaceutical Crops: An Overview, Shiyou Li, Wei Yuan, Peiying Yang, Mikhail Antoun, Michael Balick, Gordon Cragg

Faculty Publications

Pharmaceutical crops is an ambiguous term used by biologists and chemists for different categories of plants. We define pharmaceutical crops as those cultivated species that are used for extraction or preparation of therapeutic substances such as active pharmaceutical ingredients (APIs), excipients used in pharmaceutical formulations, vaccines and antibodies, as well as other therapeutic proteins. Based on the type of pharmaceutical product, these crops can be classified into three distinct yet sometimes overlapping categories: crops for the production of small therapeutic molecules (STMs), large therapeutic molecules (LMTs), or standard therapeutic extracts (STEs). This review briefly discusses the relationships of pharmaceutical crops …

An Overview Of Genus Aesculus L.: Ethnobotany, Phytochemistry, And Pharmacological Activities, Shiyou Li, Xiao-Yuan Lian, Zhizhen Zhang

Faculty Publications

The genus Aesculus L. (Hippocastanaceae) has 12 species distributed in eastern Asia, eastern and western North America, and Europe. In Europe and the United States, A. hippocastanum has been used for the treatment of chronic venous insufficiency, hemorrhoids, and postoperative edema. In China, A. chinensis var. chinense has been used as a stomachic and analgesic in the treatment of distention and pain in the chest and the abdomen, malaria, dysentery, and heart disease. The objective of this paper is to review the ethnobotany, phytochemistry, and pharmacological properties of the genus Aesculus. To date, more than 210 compounds have been isolated …

Studies Of Antioxidant And Angiotensin Converting Enzyme Inhibitory Activity Of Orthosiphon Stamineus (Misai Kucing)., Che Wan Imanina Che Wan Takwa

Student Works (2010-2019)

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Marine Algae As A Source Of Photosensitisers For Photodynamic Therapy Of Cancer., Tang Yee Voon

Student Works (2010-2019)

Photodynamic therapy (PDT) involves the intravenous administration of a photosensitiser that preferentially localises in cancerous tissues more than the surrounding normal tissues. Subsequent illumination of photosensitiser generates reactive oxygen species that cause irreversible photo-damage to the cancer cells. To date, most photosensitisers that have been approved for clinical use or are currently in clinical trials are cyclic tetrapyrroles which are derived or inspired by naturally occurring chlorophyll and its degradation products. Some non-tetrapyrrolic photosensitisers have also been found in nature suggesting that there are potential photosensitisers with interesting structures in nature. To this end, this thesis outlines the collection of …

Bioactivity And Chemical Investigations Of Pereskia Bleo And Pereskia Grandifollia., Sim Kae Shin

Student Works (2010-2019)

Ethnopharmacological data has been one of the common useful criteria in drug discovery. Pereskia bleo and Pereskia grandifolia (Cactaceae), commonly known as ‘Jarum Tujuh Bilah’ in Malay and ‘Cak Sing Cam’ in Chinese have long been used as natural remedies in Malaysia. The experimental approach in the present study was based on bioassay-guided fractionation. The crude methanol and fractionated extracts of both Pereskia spp. were initially investigated for their biological activities such as antioxidant, antimicrobial and cytotoxic effect against five human cancer cell lines, namely nasopharyngeal epidermoid carcinoma cell line (KB), cervical carcinoma cell line (CasKi), colon carcinoma cell line …

Chemical Constituents Of Cryptocarya Densiflora., Nurul Nazneem Wan Othman

Student Works (2010-2019)

The extraction of alkaloids from the Malaysian Cryptocarya densiflora has been carried out in this study. The alkaloids were extracted from the bark and leaves of this species using acid base extraction and the crude alkaloids obtained were subjected to extensive chromatographic techniques such as thin layer and column chromatography. The structural elucidation of the purified alkaloids were performed with the aid of spectroscopic methods i.e. 1H NMR, 13C NMR, 2D NMR, IR, UV and LCMS. Investigation of the alkaloidal content from the bark of Cryptocarya densiflora afforded six alkaloids and their structures were elucidated as laurotetanine 63, isocaryachine 64, …

The Nonpsychoactive Cannabinoid Cannabidiol Inhibits 5-Hydroxytryptamine3a Receptor-Mediated Currents In Xenopus Laevis Oocytes, Keun-Hang Susan Yang, Sehamuddin Galadari, Dmytro Isaev, Georg Petroianu, Toni S. Shippenberg, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

The effect of the plant-derived nonpsychotropic cannabinoid, cannabidiol (CBD), on the function of hydroxytryptamine (5-HT)3A receptors expressed in Xenopus laevis oocytes was investigated using two-electrode voltage-clamp techniques. CBD reversibly inhibited 5-HT (1 μM)-evoked currents in a concentration-dependent manner (IC50 = 0.6 μM). CBD (1 μM) did not alter specific binding of the 5-HT3A antagonist [3H]3-(5-methyl-1H-imidazol-4-yl)-1-(1-methylindol-3-yl)propan-1-one (GR65630), in oocytes expressing 5-HT3A receptors. In the presence of 1 μM CBD, the maximal 5-HT-induced currents were also inhibited. The EC50 values were 1.2 and 1.4 μM, in the absence and presence of CBD, indicating that CBD acts as a noncompetitive antagonist of 5-HT3 …