In-silico analysis and transformation of OsMYB48 transcription factor driven by CaMV35S promoter in model plant - Nicotiana tabacum L. conferring abiotic stress tolerance.

Global crop yield has been affected by a number of abiotic stresses. Heat, salinity, and drought stress are at the top of the list as serious environmental growth-limiting factors. To enhance crop productivity, molecular approaches have been used to determine the key regulators affecting stress-related phenomena. MYB transcription factors (TF) have been reported as one of the promising defensive proteins against the unfavorable conditions that plants must face. Different roles of MYB TFs have been suggested such as regulation of cellular growth and differentiation, hormonal signaling, mediating abiotic stress responses, etc. To gain significant insights, a comprehensive in-silico analysis of OsMYB TF was carried out in comparison with 21 dicot MYB TFs and 10 monocot MYB TFs. Their chromosomal location, gene structure, protein domain, and motifs were analyzed. The phylogenetic relationship was also studied, which resulted in the classification of proteins into four basic groups: groups A, B, C, and D. The protein motif analysis identified several conserved sequences responsible for cellular activities. The gene structure analysis suggested that proteins that were present in the same class, showed similar intron-exon structures. Promoter analysis revealed major cis-acting elements that were found to be responsible for hormonal signaling and initiating a response to abiotic stress and light-induced mechanisms. The transformation of OsMYB TF into tobacco was carried out using the Agrobacterium-mediated transformation method, to further analyze the expression level of a gene in different plant parts, under stress conditions. To summarize, the current studies shed light on the evolution and role of OsMYB TF in plants. Future investigations should focus on elucidating the functional roles of MYB transcription factors in abiotic stress tolerance through targeted genetic modification and CRISPR/Cas9-mediated genome editing. The application of omics approaches and systems biology will be indispensable in delineating the regulatory networks orchestrated by MYB TFs, facilitating the development of crop genotypes with enhanced resilience to environmental stressors. Rigorous field validation of these genetically engineered or edited crops is imperative to ascertain their utility in promoting sustainable agricultural practices.

Mechanistic insight into the protective effects of fisetin against arsenic-induced reproductive toxicity in male rats.

Arsenic is one of the most hazardous environmental contaminants, which adversely affects the dynamics of male reproductive system. Fisetin (FIS) is a bioactive flavonoid, which is known to exert strong antioxidative effects. Therefore, the current research was planned to evaluate the alleviative efficacy of FIS against arsenic-induced reproductive damages. Forty-eight male albino rats were divided into 4 groups (n = 12), which were treated as follows: (1) Control, (2) Arsenic-intoxicated group (8 mg kg-1), (3) Arsenic + FIS-treated group (8 mg kg-1 + 10 mg kg-1), and (4) FIS-treated group (10 mgkg-1). After 56 days of treatment, the biochemical, lipidemic, steroidogenic, hormonal, spermatological, apoptotic and histoarchitectural profiles of rats were analyzed. Arsenic intoxication reduced the enzymatic activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GSR), in addition to glutathione (GSH) level. Conversely, the levels of thiobarbituric acid reactive substance (TBARS) and reactive oxygen species (ROS) were increased. Moreover, it escalated the level of low-density lipoprotein (LDL), triglycerides and total cholesterol, while declining the level of high-density lipoprotein (HDL). Furthermore, steroidogenic enzymes expressions, 3ß-hydroxysteroid dehydrogenase (HSD), 17ß-HSD, steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (CYP11A1) and 17α-hydroxylase/17, 20-lyase (CYP17A1), were found to be reduced, which brought down the level of testosterone. Besides, the levels of gonadotropins (LH and FSH) were decreased. Additionally, a decline in sperm mitochondrial membrane potential (MMP), motility, epididymal sperm count and hypo-osmotic swelling (HOS) coil-tailed sperms was observed, whereas the dead sperms and structural damages (head, midpiece and tail) of sperms were escalated. Moreover, arsenic exposure up-regulated the mRNA expressions of apoptotic markers, namely Bax and caspase-3, whereas lowered the expression of anti-apoptotic marker, Bcl-2. In addition, it induced histoarchitectural changes in testes of rats. However, FIS treatment resulted in remarkable improvements in testicular and sperm parameters. Therefore, it was inferred that FIS could serve as a therapeutic candidate against arsenic-generated male reproductive toxicity attributing to its anti-oxidant, anti-lipoperoxidative, anti-apoptotic, and androgenic efficacy.

Utility of fatty acid profile and in vitro immune cell activation for chemical and biological standardization of Arthrospira/Limnospira.

Commercially cultivated Limnospira (species formerly classified to genus Arthrospira) is a popular food/supplement consumed by millions of people worldwide for health benefits. The objective of the current research was to advance the standardization technology for Limnospira. Quantitative methods were established to detect fatty acids as potential chemical markers and immune-enhancing activity. Analysis of 20 different batches of biomass obtained from one commercial grower demonstrated that there was a statistically significant relationship between the sum of two fatty acids (linoleic and γ-linolenic) and Toll-like receptor (TLR)2/TLR1-dependent activation (R2 = 0.48, p = 0.0007). Investigation of 12 biomass samples sourced from growers in 10 different countries demonstrated that fatty acid content was again significantly correlated with biological activity (R2 = 0.72, p = 0.0005) and the content of fatty acids varied by twofold and activity by 12.5-fold. This large variation between different samples confirms the need to use the present standardization methods to ensure consistent and properly characterized biomass for consumers and for future scientific research.

Computational Tools to Expedite the Identification of Potential PXR Modulators in Complex Natural Product Mixtures: A Case Study with Five Closely Related Licorice Species.

The genus Glycyrrhiza, comprising approximately 36 spp., possesses complex structural diversity and is documented to possess a wide spectrum of biological activities. Understanding and finding the mechanisms of efficacy or safety for a plant-based therapy is very challenging, yet it is crucial and necessary to understand the polypharmacology of traditional medicines. Licorice extract was shown to modulate the xenobiotic receptors, which might manifest as a potential route for natural product-induced drug interactions. However, different mechanisms could be involved in this phenomenon. Since the induced herb-drug interaction of licorice supplements via Pregnane X receptor (PXR) is understudied, we ventured out to analyze the potential modulators of PXR in complex mixtures such as whole extracts by applying computational mining tools. A total of 518 structures from five species of Glycyrrhiza: 183 (G. glabra), 180 (G. uralensis), 100 (G. inflata), 33 (G. echinata), and 22 (G. lepidota) were collected and post-processed to yield 387 unique compounds. Visual inspection of top candidates with favorable ligand-PXR interactions and the highest docking scores were identified. The in vitro testing revealed that glabridin (GG-14) is the most potent PXR activator among the tested compounds, followed by licoisoflavone A, licoisoflavanone, and glycycoumarin. A 200 ns molecular dynamics study with glabridin confirmed the stability of the glabridin-PXR complex, highlighting the importance of computational methods for rapid dereplication of potential xenobiotic modulators in a complex mixture instead of undertaking time-consuming classical biological testing of all compounds in a given botanical.

Analyzing the regulatory role of heat shock transcription factors in plant heat stress tolerance: a brief appraisal.

An increase in ambient temperature throughout the twenty-first century has been described as a "worldwide threat" for crop production. Due to their sessile lifestyles, plants have evolved highly sophisticated and complex heat stress response (HSR) mechanisms to respond to higher temperatures. The HSR allows plants to minimize the damages caused by heat stress (HS), thus enabling cellular protection. HSR is crucial for their lifecycle and yield, particularly for plants grown in the field. At the cellular level, HSR involves the production of heat shock proteins (HSPs) and other stress-responsive proteins to counter the negative effects of HS. The expression of most HSPs is transcriptionally regulated by heat shock transcription factors (HSFs). HSFs are a group of evolutionary conserved regulatory proteins present in all eukaryotes and regulate various stress responses and biological processes in plants. In recent years, significant progress has been made in deciphering the complex regulatory network of HSFs, and several HSFs not only from model plants but also from major crops have been functionally characterized. Therefore, this review explores the progress made in this fascinating research area and debates the further potential to breed thermotolerant crop cultivars through the modulation of HSF networks. Furthermore, we discussed the role of HSFs in plant HS tolerance in a class-specific manner and shed light on their functional diversity, which is evident from their mode of action. Additionally, some research gaps have been highlighted concerning class-specific manners.

Unfolding molecular switches in plant heat stress resistance: A comprehensive review.

KEY MESSAGE: Plant heat stress response is a multi-factorial trait that is precisely regulated by the complex web of transcription factors from various families that modulate heat stress responsive gene expression. Global warming due to climate change affects plant growth and development throughout its life cycle. Adds to this, the frequent occurrence of heat waves is drastically reducing the global crop yield. Molecular plant scientists can help crop breeders by providing genetic markers associated with stress resistance. Plant heat stress response (HSR), however, is a multi-factorial trait and using a single stress resistance trait might not be ideal to develop thermotolerant crops. Transcription factors participate in regulation of plant biological processes and environmental stress responses. Recent studies have revealed that plant HSR is precisely regulated by the complex web of transcription factors from various families. These transcription factors enhance plant heat stress tolerance by regulating the expression level of several stress-responsive genes independently or in cross talk with different other transcription factors. This review explores how signaling pathways triggered by heat stress are regulated by multiple transcription factor families. To our knowledge, we for the first time analyze the role of major transcription factor families in plant HSR along with their regulatory mechanisms. In the end, we will also discuss the potential of emerging technologies to improve thermotolerance in plants.

Balancing the efficacy vs. the toxicity of promiscuous natural products: Paclitaxel-based acid-labile lipophilic prodrugs as promising chemotherapeutics.

TumorSelect® is an anticancer technology that combines cytotoxics, nanotechnology, and knowledge of human physiology to develop innovative therapeutic interventions with minimal undesirable side effects commonly observed in conventional chemotherapy. Tumors have a voracious appetite for cholesterol which facilitates tumor growth and fuels their proliferation. We have transformed this need into a stealth delivery system to disguise and deliver anticancer drugs with the assistance of both the human body and the tumor cell. Several designer prodrugs are incorporated within pseudo-LDL nanoparticles, which carry them to tumor tissues, are taken up, internalized, transformed into active drugs, and inhibit cancer cell proliferation. Highly lipophilic prodrug conjugates of paclitaxel suitable for incorporation into the pseudo-LDL nanoparticles of the TumorSelect® delivery vehicle formulation were designed, synthesized, and evaluated in the panel of 24-h NCI-60 human tumor cell line screening to demonstrate the power of such an innovative approach. Taxane prodrugs, viz., ART-207 was synthesized by tethering paclitaxel to lipid moiety with the aid of a racemic solketal as a linker in cost-effective, simple, and straightforward synthetic transformations. In addition to the typical 24-h NCI screening protocol, these compounds were assessed for growth inhibition or killing of ovarian cell lines for 48 and 72h-time intervals and identified the long-lasting effectiveness of these lipophilic prodrugs. All possible, enantiomerically pure isomers of ART-207 were also synthesized, and cytotoxicities were biosimilar to racemic ART-207, suggesting that enantiopurity of linker has a negligible effect on cell proliferation. To substantiate further, ART-207 was evaluated for its in vivo tumor reduction efficacy by studying the xenograft model of ovarian cancer grown in SCID mice. Reduced weight loss (a measure of toxicity) in the ART-207 group was observed, even though it was dosed at 2.5x the paclitaxel equivalent of Abraxane®. As a result, our delineated approach is anticipated to improve patient quality of life, patient retention in treatment regimes, post-treatment rapid recovery, and overall patient compliance without compromising the efficacy of the cytotoxic promiscuous natural products.

Cis-trimethoxystilbene, exhibits higher genotoxic and antiproliferative effects than its isomer trans-trimethoxystilbene in MCF-7 and MCF-10A cell lines.

Stilbenes are a class of natural compounds with a wide variety of biological effects, such as antitumor activity. The best-known stilbene is resveratrol, whose clinical application is limited due to its low bioavailability. Methoxylated derivatives of this stilbene, including cis-trimethoxystilbene (cis-TMS) and trans-trimethoxystilbene (trans-TMS) have demonstrated more pronounced cytotoxic and anti-proliferative effects than resveratrol. Thus, the objective of this study is to evaluate and compare the cytotoxicity and antiproliferative effects of cis- and trans-TMS in MCF-7 and its normal counterpart MCF-10A. Both compounds were cytotoxic, genotoxic, and induced G2-M accumulation and cell death in the two cell lines. These results suggested that the genotoxicity of cis- and trans-TMS is involved in the reduction of cellular proliferation of MCF-7 and MCF-10A cells, but notably, such antiproliferative effects are more pronounced for cis- than trans-TMS.

Novel Machaeriol Analogues as Modulators of Cannabinoid Receptors: Structure-Activity Relationships of (+)-Hexahydrocannabinoids and Their Isoform Selectivities.

Machaeriols are an important class of compounds that structurally resemble tetrahydrocannabinol (Δ9-THC), with the major differences being inverted stereochemistry at the ring junction as [6aR, 10aR] and an additional stereocenter at the C9 position of the A-ring due to saturation. A previous study reported that machaeriols did not show any cannabinoid receptor activity, even though these hexahydrodibenzopyran analogues mimic a privileged (+)-tetrahydrocannabinoid scaffold. To unravel structural requisites for modulation of cannabinoid receptors, a simple late-stage divergent approach was undertaken to functionalize the machaeriol scaffold using the Suzuki coupling reaction. Fourteen hexahydro analogues were synthesized and screened against both cannabinoid receptor isoforms, CB1 and CB2. Interestingly, many of the analogues showed a significant binding affinity for both receptors; however, two analogues, 11H and 11J, were identified as possessing CB2 receptor-selective functional activity in the GTPγS assay; they were found to be micromolar-range agonists, with EC50 values of 5.7 and 16 µM, respectively. Furthermore, molecular dynamics simulations between the CB2 receptor and two novel analogues resulted in unique interaction profiles by tightly occupying the active ligand-binding domain of the CB2 receptor and maintaining stable interactions with the critical residues Phe94, Phe281, and Ser285. For the first time, with the aid of structure-activity relationships of (+)-hexahydrocannabinoids, CB2 selective agonists were identified with late-stage diversification using palladium-mediated C-C bond formation. By simply switching to (R)-citronellal as a chiral precursor, enantiomerically pure (-)-hexahydrocannabinoids with better CB1/CB2 receptor isoform selectivity can be obtained using the current synthetic approach.

Molecular mechanisms of plant tolerance to heat stress: current landscape and future perspectives.

KEY MESSAGE: We summarize recent studies focusing on the molecular basis of plant heat stress response (HSR), how HSR leads to thermotolerance, and promote plant adaptation to recurring heat stress events. The global crop productivity is facing unprecedented threats due to climate change as high temperature negatively influences plant growth and metabolism. Owing to their sessile nature, plants have developed complex signaling networks which enable them to perceive changes in ambient temperature. This in turn activates a suite of molecular changes that promote plant survival and reproduction under adverse conditions. Deciphering these mechanisms is an important task, as this could facilitate development of molecular markers, which could be ultimately used to breed thermotolerant crop cultivars. In current article, we summarize mechanisms involve in plant heat stress acclimation with special emphasis on advances related to heat stress perception, heat-induced signaling, heat stress-responsive gene expression and thermomemory that promote plant adaptation to short- and long-term-recurring heat-stress events. In the end, we will discuss impact of emerging technologies that could facilitate the development of heat stress-tolerant crop cultivars.

In search for potential antidiabetic compounds from natural sources: docking, synthesis and biological screening of small molecules from Lycium spp. (Goji).

Current clinical antidiabetic drugs, like rosiglitazone 1, have been implicated in some serious side effects like edema, weight gain, and heart failure, making it necessary to find alternative agents. Partial agonists of peroxisome-proliferator activated receptor-gamma (PPARγ) were determined to possess improved insulin sensitivity without undeseirable side-effects when compared to full agonists of PPARγ, like rosiglitazone 1. The traditional Chinese medicine (TCM) plants, Goji (Lycium barbarum and Lycium chinense) are widely used for treating symptoms related to various diseases including diabetes and hypertension. Twenty-seven reported compounds from Goji were docked into both partial- and full-agonist binding sites of PPARγ. Amongst the docked compounds, phenylethylamide-based phytochemicals (5-9) (termed as tyramine-derivatives, TDs) were found to possess good docking scores and binding poses with favorable interactions. Synthesis of 24 TDs, including three naturally occuring amides (6, 8, 9) were synthesized and tested for PPARγ gene induction with cell-based assay. Three compounds showed similar or higher fold induction than the positive control, rosiglitazone. Among these three active TDs, trans-N-feruloyloctopamine (9) and tyramine derivatives-enriched extract (TEE) (21%) of the root bark of L. chinense were further studied in vivo using db/db mice. However, both TEE as well as 9 did not show significant antidiabetic properties in db/db mice. In vivo results suggest that the proposed antidiabetic property of Lycium species may not be due to tyramine derivatives alone. Further studies of tyramine derivatives or enriched extract(s) for other bioactivities like hypocholesterolemic activities, and studies of novel isolated compounds from Goji will enable a more complete understanding of their bioactivities.

Synthesis of benzonaphthofuroquinones and benzoylnaphthindolizinediones by reactions of flavonoids with dichlone under basylous, oxygenous and aqueous conditions: their cytotoxic and apoptotic activities.

Using flavonoids and dichlone as substrates, benzonaphthofuroquinones (1, 2, 3, 5, 6, novel; 4 new) and benzoylnaphthindolizinediones (7, 8, known; 9, new) were synthesized through common base-catalyzed method and a new method of combining base-catalyzed with O2/H2O exposing. The possible reaction mechanisms may involve the process like isomerization, hydration, oxidation, decomposition and intermolecular condensation. Benzonaphthofuroquinones (2, 3, 4, 5) were found to exhibit potent cytotoxicity against carcinoma cell lines and low toxicity to normal cell lines. The compounds 4 and 5 not only expressed a significant late-stage-apoptosis against human leukemia and melanoma, but also promoted the cleavage of caspase-3 and PARP in human leukemia, which suggested that the late-stage-apoptosis and caspase-3 pathway may be responsible for the cytotoxicities of these benzonaphthofuroquinones. The replacement of the furan ring with pyrrole system in benzoylnaphthindolizinediones (7, 8, 9) resulted in the loss of anticancer activity.

Green chemistry appended synthesis, metabolic stability and pharmacokinetic assessment of medicinally important chromene dihydropyrimidinones.

A green chemistry approach has been developed for the synthesis of chromene dihydropyrimidinone (CDHPM) using recyclable Fe/Al pillared clay catalyst. Pharmacokinetic parameters like aqueous solubility, lipophilicity, P-glycoprotein (P-gp) ATPase activity, permeability, plasma protein binding, red blood cell (RBC) partitioning, metabolic stability in liver microsomes and in silico computations have been studied for the most potent anticancer chromene dihydropyrimidinone hybrid 1. This compound exhibited low solubility, optimum lipophilicity, no P-gp inhibitory activity, intermediate permeability, high plasma protein binding, low RBC partitioning, acceptable metabolic stability in rat liver microsomes (RLM) as well as human liver microsomes (HLM) with transitional hepatic extraction ratio.

Design, synthesis and biological evaluation of benzoxazolinone-containing 1,3,4-thiadiazoles as TNF-α inhibitors.

A library of nineteen benzoxazolinone-based 1,3,4-thiadiazoles has been synthesized and screened for their anti-inflammatory activity. The compound 1f exhibited a potent anti-inflammatory activity with an inhibition of 65.83% and 32.50% after 3 h and 5 h respectively. It also exhibited a significant in vitro (p < 0.01), TNF- α inhibitory activity with 51.44 % inhibition. The compound 1f showed hydrogen bonding with GLN 61 and interactions with TYR 119, TYR 151 and GLY 121. The histopathology report showed that none of the compounds caused gastric ulceration. The results from the in vivo & in vitro antiinflammatory activity along with In Silico studies exhibit that benzoxazolinone-based 1,3,4-thiadiazoles may be used in the future development of anti-inflammatory drugs.

Utility of alkaloids as chemical and biomarkers for quality, efficacy, and safety assessment of botanical ingredients.

BACKGROUND: Selecting the appropriate chemical and bio-markers for monitoring the quality, efficacy, and safety is critical for efficient and reliable assessment of traditional medicines derived from botanical sources. Chemical markers have been implicated primarily in establishing the analytical methodologies aiming at verification of the botanical sources of the raw materials, the extracts, and the finished products such as botanical dietary supplements and nutraceuticals. In addition, they have been employed in differentiation between crude or raw (unprocessed) and processed plant extracts, and identification as well as determination of potential toxicants and adulterants in herbal medicines. Additionally, these chemical markers are utilized for selection of efficient methods for extraction of plants. Further, biomarkers have been exploited in determination of the pharmacokinetic properties of bioactive herbal constituents. Alkaloids, unlike other plant constituents, are uniquely characterized by having basic properties, and possessing substantial and diverse pharmacological effects. These features make alkaloids attractive components for functioning as chemical and biomarkers in determining the quality of botanical ingredients where this class of phytochemicals prevail or is responsible for lending biological effects. PURPOSE: The aim of the review is to exhibit the function of alkaloids as biomarkers and chemical markers in the evaluation of quality, efficacy, and safety of medicinal herbs and their commercial products. METHODS: Literature acquisition was accomplished using the most commonly accessed scholarly search engines including SciFinder, PubMed, and Google Scholar. Secondly, the full-texts which are relevant to the topic were included in this review. This was followed by a thorough and detailed analysis of the collected information. RESULTS: The literature search with main emphasis on the roles of alkaloids in the evaluation of quality, efficacy and safety of herbal medicines was evaluated to provide all succinct information in one place. Compilation of such critical information is expected to help the reader to appreciate alkaloids as important markers in the quality control of herbal drugs and products. CONCLUSION: The current review article covers the fundamental roles played by alkaloids as chemical and biomarkers in assessing the essential parameters of the quality of botanical ingredients, as briefly described earlier. The utilization of alkaloids as biomarkers to determine the efficacy-linked pharmacokinetic parameters is limited to reviewing studies on human subjects.

Pharmacokinetics and Tissue Distribution of Aegeline after Oral Administration in Mice.

Aegeline is claimed to be a biologically active constituent of Aegle marmelos. Preclinical studies have reported possible therapeutic potential for aegeline against obesity and diabetes. In recent years, aegeline has been added to several weight loss products. However, the consumption of aegeline-containing supplements such as OxyELITE Pro and VERSA-1 has been linked to multiple cases of acute and chronic liver failure. This study was carried out to evaluate the pharmacokinetics and tissue distribution of aegeline in ND4 mice. Two doses of aegeline, a human equivalent dose (1×) 30 mg/kg and a 10× dose (300 mg/kg), were orally administered to the mice, and blood and tissue samples were collected over 8 h. The quantitative analysis of plasma and tissue homogenates (liver, kidney, and brain) was done by UHPLC-QTOF to determine aegeline concentrations. The peak plasma level of aegeline was achieved at a Tmax of 0.5 h, indicating its rapid absorption from the gastrointestinal tract. Aegeline was not detected in the plasma at 8 h after oral administration, with a half-life of 1.4 ± 0.01 and 1.3 ± 0.07 h for the 30 and 300 mg/kg doses, respectively. The half-life of aegeline in the liver was 1.2 h and 1.7 h for 30 and 300 mg/kg doses, respectively, with a Tmax of 1.9 h, which indicates relatively fast elimination of aegeline from the liver.

The power of hyphenated chromatography-Time of flight mass spectrometry for unequivocal identification of spirostanes in bodybuilding dietary supplements.

A previously unidentified purported botanical ingredient was found in dietary supplements marketed for anabolic benefits. In an attempt to assess the 'naturalness' of a group of steroid-like compounds called laxogenins, a UHPLC-QToF method was developed. Several dietary supplements claim to contain 5α-hydroxy laxogenin, which is a derivative of a naturally occurring spirostane-type steroid, laxogenin. Although laxogenin has been isolated from the rhizomes of Smilax sieboldii, 5α-hydroxy laxogenin has not been isolated or reported from any natural source. These derivatives of laxogenins have untested anabolic properties. Due to the low UV absorbance of the spirostanes, a mass spectrometric method in positive ion mode was developed for unambiguous identification of laxogenin and closely related compounds. To show the utility of the developed method, twelve dietary supplements labeled to contain 5α-hydroxy laxogenin or laxogenin as 5α-hydroxy laxogenin were analyzed as a proof-of-concept. Five supplements did not contain any 5α-hydroxy laxogenin, whereas in the remaining seven samples, spirostane-type contaminants were identified along with the labeled 5α-hydroxy laxogenin. The identity of some of these contaminants was established based on reference standards along with mass fragmentation patterns. One of the unlabeled contaminants was identified as the phytosteroid saponin, diosgenin, a common starting precursor of several steroidal drugs. Several synthetic derivatives of diosgenin were identified in the eight products. These findings indicate that the labeled 5α-hydroxy laxogenin along with other spirostanes found in supplements are synthetic and signify a lack of quality controls. Additionally, an unlabeled, anabolic androgenic steroid, arimistane, an aromatase inhibitor, was also identified in one product. Laxogenin, was not detected in any of the samples analyzed during this investigation.

Overview of Analytical Tools for the Identification of Adulterants in Commonly Traded Herbs and Spices.

Background: Spices and aromatic herbs have long been used by people to impart sensory appetizing elements, including aroma, flavor, and color, to foods and beverages in an effort to enhance their palatability. Herbs and spices exhibit a plethora of medicinal properties including antimicrobial and antioxidant properties. Spices serve as natural preservatives to delay food spoilage and extend shelf life. As spice trading has exponentially increased globally, herbs and spices have become prone to adulteration, which can be deliberate or unintentional. Deliberate adulteration is usually economically motivated, aimed at maximizing profit margins, whereas unintentional adulteration is often attributed to improper harvesting or processing of the plant material or collecting/substituting closely related species. Adulteration of herbs or spices with toxic ingredients such as Sudan dyes or metal salts (e.g., lead chromate) may result in serious public health consequences. Objective: To provide a concise account of ongoing adulteration issues with spices and herbs in order to enhance general awareness of the short- and longer-term implications of such fraud. Method: Last twenty-years of literature on various aspects of spice adulteration including text books and online resources were gathered and compiled. In addition, a number of original reports have been published prior to year 2000 that are directly associated with adulteration of commonly traded herbs and spices were also included. Results: The current review covers the role of spices and herbs in human life, adulteration of the commonly consumed spices and herbs, identification of their adulterants, as well as the most popular analytical techniques and methods used in their detection, including spectroscopic, chromatographic, electronic sensing, and deoxyribonucleic acid-based methodologies. Conclusions: Spices and herbs, being high-priced commodities, have been often subjected to adulteration in many ways which reduces their quality and potentially has harmful health implications. Adulteration is attributed primarily to increased demand or supply shortage of the spices and aromatic herbs. The motivation for spice fraud is largely attributed to economical interest to gain greater profit margins and such adulteration of spices can have serious implications for public health. To combat the adulteration of spices and herbs effectively, a range of analytical techniques across many different technologies have been developed. These techniques are expected to aid in the detection of adulterants and establish quantifiable concentrations for the compounds in question in various matrices, including spices and aromatic herbs.

Impact of obesity on the toxicity of a multi-ingredient dietary supplement, OxyELITE Pro™ (New Formula), using the novel NZO/HILtJ obese mouse model: Physiological and mechanistic assessments.

Herbal dietary supplement (HDS)-induced hepato- and cardiotoxicity is an emerging clinical problem. In this study, we investigated the liver and heart toxicity of HDS OxyELITE-PRO™ New Formula (OEP-NF), a dietary supplement marketed for weight loss and performance enhancement that was recently withdrawn from the market. Using a novel NZO/HlLtJ obese mouse model, we demonstrated that administration of clinically relevant mouse equivalent doses (MED) of OEP-NF produced cardio- and hepatotoxic risks following both short- and long-term administration schedules. Specifically, gavaging female NZO/HlLtJ with up to 2X MED of OEP-NF resulted in 40% mortality within two weeks. Feeding mice with either 1X or 3X MED of OEP-NF for eight weeks, while not exhibiting significant effects on body weights, significantly altered hepatic gene expression, increased the number of apoptotic and mast cells in the heart and affected cardiac function. The degree of toxicity in NZO/HlLtJ mice was higher than that observed previously in non-obese CD-1 and B6C3F1 strains, suggesting that an overweight/obese condition can sensitize mice to OEP-NF. Adverse health effects linked to OEP-NF, together with a number of other hepato- and cardiotoxicity cases associated with HDS ingestion, argue strongly for introduction of quality standards and pre-marketing safety assessments for multi-ingredient HDS.

One-step, stereoselective synthesis of octahydrochromanes via the Prins reaction and their cannabinoid activities.

Novel, functionalized octahydrochromene derivatives were synthesized in a single step via the Prins reaction. Enantiomerically pure (+)-isopulegol was reacted with benzaldehyde to stereoselectively yield the corresponding octahydro-2H-chromen-4-ol derivative containing five stereocenters. A total of 10 compounds were synthesized by altering the enantiomer of isopulegol and the substituted benzaldehyde, and the resulting enantiopure octahydrochromenes were screened in vitro against the cannabinoid receptor isoforms CB1 and CB2. Compounds containing an olefin at the C4 position [(+)-3c, (-)-3c, (-)-7c, (-)-9c and (-)-11c] of the octahydrochromene scaffold were found to exhibit reasonable displacement of [3H] CP55,940 from the CB receptors, whereas the corresponding hydroxy analogs [(+)-3a, (+)-3b, (-)-3a, (-)-3b and (+)-5a] had very little or no effect.