Acute, Subchronic, and Genetic Toxicity Assessments of a Composition of Fruit Rind and Seed Extracts.

LN19183 is a standardized composition of (Christm) Swingle (CA) fruit rind and L. (TC) seed extracts that have recently been demonstrated to increase resting energy expenditure (REE) and reduce body fat in rats. CA and TC are important herbs in traditional medicine for various health benefits.

A Synergistic Botanical Composition Increases Resting Energy Expenditure and Reduces Adiposity in High-Fat Diet-Fed Rats.

Objective: An imbalance between dietary energy intake and energy expenditure may result in body fat gain or obesity. Increasing resting energy expenditure (REE) is an attractive strategy for managing body fat gain. The objective of the current study was to generate proof-of-concept data on a synergistic composition (LN19183) of fruit rind (CA) and seed (TC) extracts to increase REE and reduce body fat gain in a high-fat diet (HFD)-fed rats.

A synergistic blend of fruit rind and leaf extracts enhances myogenic differentiation and mitochondrial biogenesis and muscle growth and strength in mice.

Background: A proprietary combination of fruit rind and leaf extracts (LI80020F4, CinDura) improved the physical performance and muscle strength of resistance-trained adult males.

Objective: This study assessed the underlying mechanisms of the ergogenic potential of LI80020F4 in and models.

Methods: The individual extracts and their combination (LI80020F4) were assessed for nitrite production in EAhy926 human endothelial cells.

Toxicological Assessments of a Proprietary Blend of Fruit Rind and Seed Extracts: Acute, Subchronic, and Genetic Toxicity Studies.

LN18178 (Tesnor) is a standardized, proprietary composition of aqueous ethanol extracts of fruit rind and seeds. The present study demonstrates a broad-spectrum toxicological evaluation of LN18178 utilizing and preclinical models following the Organization for Economic Cooperation and Development (OECD) guidelines for testing chemicals. Wistar rats did not show any clinical signs of toxicity and morbidity in acute oral and dermal toxicity tests with the median lethal dose (LD) values of at least 5000 mg/kg and 2000 mg/kg body weight, respectively.

Safety assessment of a novel water-soluble extract of gum resin: acute toxicity, 90-day sub-chronic toxicity, Ames' bacterial reverse mutation, and micronucleus assays.

gum resin extracts have demonstrated potential benefits in alleviating joint pain and discomfort of osteoarthritis. The major objective of the present study was to assess the safety of a water-soluble gum resin extract (LI51202F1) in diverse models of acute oral, acute dermal, primary dermal irritation, eye irritation, and 90-day sub-chronic repeated dose toxicity studies, as well as Ames' bacterial reverse mutation assay and micronucleus assay. The acute oral and dermal toxicity studies in (SD) rats demonstrated that the median lethal dose (LD) of LI51202F1 is >2000 mg/kg body weight (BW).

Combined extracts of Moringa oleifera, Murraya koeingii leaves, and Curcuma longa rhizome increases energy expenditure and controls obesity in high-fat diet-fed rats.

Background: LI85008F is a proprietary combination of leaf extracts of Moringa oleifera, Murraya koeingii, and extract of Curcuma longa rhizome. This herbal extract combination is an effective weight loss supplement for overweight and obese subjects. The present study aimed to investigate the thermogenic potential of the LI85008F in high-fat diet (HFD)-induced obese Sprague Dawley rats.

Acute, Subacute, and Genotoxicity Assessments of a Proprietary Blend of Fruit Rind and Leaf Extracts (CinDura®).

The present communication describes a battery of toxicity studies that include an acute oral toxicity, a subacute twenty-eight-day repeated oral dose toxicity, and genotoxicity studies on a herbal formulation CinDura® (GMCT). This proprietary herbal composition contains the extracts of the fruit rind (GM) and the leaf (CT). The toxicological evaluations were performed following the Organization for Economic Cooperation and Development (OECD) guidelines.

An Anti-Inflammatory Composition of Resin Extracts Alleviates Pain and Protects Cartilage in Monoiodoacetate-Induced Osteoarthritis in Rats.

The boswellic acids, the active compounds in gum resin extract, are potent anti-inflammatory agents and are specific nonredox inhibitors of 5-Lipoxygenase (5-LOX). Here, we present the anti-osteoarthritis (OA) efficacy of LI13019F1 (also known as Serratrin®), a unique composition containing the acidic and nonacidic fractions of gum resin. This composition strongly inhibited 5-LOX activity with the half-maximal inhibitory concentration (IC) of 43.

Toxicological Assessment of a Standardized Gum Resin Extract.

The acidic and non-acidic fractions of gum resin extracts were combined to prepare a unique product, LI13019F1 (Serratrin). The present series of studies evaluated LI13019F1 for acute and subchronic (28-day) toxicity in Wistar rats and acute dermal and eye irritation in New Zealand white rabbits. The mutagenicity and clastogenicity of LI13019F1 were evaluated in bacteria and mouse bone marrow erythrocytes, respectively.

Synthesis, in vitro and in silico evaluation of diaryl heptanones as potential 5LOX enzyme inhibitors.

A new series of diaryl heptanones (12a-q) were synthesized and their structures were confirmed by its H, C NMR and Mass spectral data. These analogs were evaluated for their anti-oxidant activity and potential to inhibit 5-lipoxygenase. Compounds 12k and 12o showed potent in vitro 5-lipoxygenase enzyme inhibitory activity with IC values of 22.

Four new Sesquiterpenoids from Sphaeranthus indicus.

Isolation and characterisation of two new eudesmanolides, 5α-hydroperoxy-7α-hydroxy-isosphaerantholide (1) and (11α,13-dihydro-7α-hydroxyfrullanolide-13-yl)-adenine (2) from the flower heads of Sphaeranthus indicus are described. In addition, 5α-hydroxy-isosphaerantholide (3) and 11α,13-dihydro-eudesman-3,5,7-triene-6α-12-olide (4) are reported first time as a metabolite of S. indicus and as a natural product, respectively.

Synthesis of new analogs of AKBA and evaluation of their anti-inflammatory activities.

A new series of 11-keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid analogs (5, 7, 8, 10, 13, 18a-d, 27a-c, 28a-d) were synthesized by modification of hydroxyl and acid functional moieties of boswellic acids. The structures of these analogs were confirmed by spectral data analysis (H, C NMR and mass). Compounds 18b, 27a and 8 showed potent 5-lipoxygenase enzyme inhibitory activity (IC: 19.

A New Flavanone from the Leaves of Chromolaena odorata.

Chromolaena odorata (Syn: Eupatorium odoratum) is a perennial plant belonging to the Asteraceae family. Extracts of C. odorata have shown strong anti-oxidant and moderate anti-adipogenenesis activities.

Mitochondrial-targeted curcuminoids: a strategy to enhance bioavailability and anticancer efficacy of curcumin.

Although the anti-cancer effects of curcumin has been shown in various cancer cell types, in vitro, pre-clinical and clinical studies showed only a limited efficacy, even at high doses. This is presumably due to low bioavailability in both plasma and tissues, particularly due to poor intracellular accumulation. A variety of methods have been developed to achieve the selective targeting of drugs to cells and mitochondrion.

Synthesis and biological evaluation of nonaprenylsulfates.

A naturally occurring nonaprenylsulfate (1) and its synthetic analogue (2) were synthesized from substituted phenolic precursors in three steps with an overall yield of 40-45%. Both compounds exhibited potent anti-inflammatory activity against 5-lipoxygenase, and potent brine shrimp lethality. They also showed moderate anti-oxidant activity in the super oxide radical scavenging model.

Digalloylresveratrol, a novel resveratrol analog inhibits the growth of human pancreatic cancer cells.

Digalloylresveratrol (DIG) is a recently synthesized substance aimed to combine the effects of the natural polyphenolic compounds gallic acid and resveratrol, which both are excellent free radical scavengers with anticancer activity. In this study, we investigated the effects of DIG in the human AsPC-1 and BxPC-3 pancreatic adenocarcinoma cell lines. Treatment with DIG dose-dependently attenuated cells in the S phase of the cell cycle and led to a significant depletion of the dATP pool in AsPC-1 cells.

Combination effects of digalloylresveratrol with arabinofuranosylcytosine and difluorodeoxycytidine in human leukemia and pancreatic cancer cells.

Digalloylresveratrol (DIG) is a newly synthesized agent aimed to combine the biological effects of the natural compounds, gallic acid and resveratrol, which both are free radical scavengers exhibiting anticancer activity. In this study, we investigated the effects of DIG on the growth of human HL-60 leukemia cells and on the colony formation of human BxPC-3 and PANC-1 pancreatic cancer cells. DIG was applied alone and in combination with arabinofuranosylcytosine (Ara-C) or difluorodeoxycytidine (dFdC), depending on the cell line employed.

Cellular and molecular mechanisms of anti-inflammatory effect of Aflapin: a novel Boswellia serrata extract.

There is significant number of evidences suggesting the anti-inflammatory properties of gum resin extracts of Boswellia serrata containing 3-O-acetyl-11-keto-β-boswellic acid (AKBA) and their promising potential as therapeutic interventions against inflammatory diseases such as osteoarthritis (OA). Unfortunately, the poor bioavailability of AKBA following oral administration might limit the anti-inflammatory efficacy of standardized Boswellia extract(s). To address this issue, we describe a novel composition called Aflapin, which contains B.

Multifactorial anticancer effects of digalloyl-resveratrol encompass apoptosis, cell-cycle arrest, and inhibition of lymphendothelial gap formation in vitro.

Background: Digalloyl-resveratrol (di-GA) is a synthetic compound aimed to combine the biological effects of the plant polyhydroxy phenols gallic acid and resveratrol, which are both radical scavengers and cyclooxygenase inhibitors exhibiting anticancer activity. Their broad spectrum of activities may probably be due to adjacent free hydroxyl groups.

Methods: Protein activation and expression were analysed by western blotting, deoxyribonucleoside triphosphate levels by HPLC, ribonucleotide reductase activity by (14)C-cytidine incorporation into nascent DNA and cell-cycle distribution by FACS.

Neuroprotective and antiinflammatory properties of a novel demethylated curcuminoid.

A demethylated derivative of curcumin (DC; 67.8% bisdemethylcurcumin, 20.7% demethylmonodemethoxycurcumin, 5.

A double blind, randomized, placebo controlled study of the efficacy and safety of 5-Loxin for treatment of osteoarthritis of the knee.

Introduction: 5-Loxin is a novel Boswellia serrata extract enriched with 30% 3-O-acetyl-11-keto-beta-boswellic acid (AKBA), which exhibits potential anti-inflammatory properties by inhibiting the 5-lipoxygenase enzyme. A 90-day, double-blind, randomized, placebo-controlled study was conducted to evaluate the efficacy and safety of 5-Loxin in the treatment of osteoarthritis (OA) of the knee.

Methods: Seventy-five OA patients were included in the study.

Biosynthetic characterization and chemoenzymatic assembly of the cryptophycins. Potent anticancer agents from cyanobionts.

The lichen cyanobacterial symbiont Nostoc sp. ATCC 53789 and its close relative Nostoc sp. GSV 224 are prolific producers of natural products, generating >25 derivatives of the cryptophycin class of secondary metabolites.

Isolation and structure determination of cryptophycins 38, 326, and 327 from the terrestrial cyanobacterium Nostoc sp. GSV 224.

Cryptophycin-38 (2), -326 (3), and -327 (4) are three new trace constituents of the terrestrial cyanobacterium Nostoc sp. GSV 224. Cryptophycin-38 is a stereoisomer of cryptophycin-1 (1) and to date is the only naturally occurring analogue that possesses a S,S epoxide group in unit A.

A convergent approach to cryptophycin 52 analogues: synthesis and biological evaluation of a novel series of fragment a epoxides and chlorohydrins.

Cryptophycin 52 is a synthetic derivative of Cryptophycin 1, a potent antimicrotubule agent isolated from cyanobacteria. In an effort to increase the potency and water solubility of the molecule, a structure-activity relationship study (SAR) was initiated around the phenyl ring of fragment A. These Cryptophycin 52 analogues were accessed using a Wittig olefination reaction between various triphenylphosphonium salts and a key intermediate aldehyde prepared from Cryptophycin 53.

Biosynthesis of 4-methylproline in cyanobacteria: cloning of nosE and nosF genes and biochemical characterization of the encoded dehydrogenase and reductase activities.

The biosynthesis of the unusual amino acid 4-methylproline in the Nostoc genus of cyanobacteria was investigated on the genetic and enzymatic level. Two genes involved in the biosynthesis were cloned and the corresponding enzymes, a zinc-dependent long-chain dehydrogenase and a Delta(1)-pyrroline-5-carboxylic acid (P5C) reductase homologue, were overexpressed in Escherichia coli and biochemically characterized. Putative substrates were synthesized to test enzyme substrate specificities, and deuterium labeling studies were carried out to reveal the stereospecificities of the enzymatic reactions with respect to the substrates as well as to the coenzymes.