Pungent Compounds Research Articles

PungentDB: Bridging traditional Chinese medicine of medicine food homology and modern food flavor chemistry

Merging traditional Chinese medicine's (TCM) principles of medicine-food homology with modern flavor chemistry, this research unveils PungentDB (http://www.pungentdb.org.cn/home), a database documenting 205 unique pungent flavor compounds from 231 TCMs. It provides detailed insights into their chemical attributes, biological targets (including IC50/EC50 values), and molecular structures (2D/3D), enriched with visualizations of target organ distribution and protein structures, exploring the pungent flavor space with the help of a feature-rich visual interface. This collection, derived from over 3249 sources and highlighting 9129 targets, delves into the compounds' unique pungent flavors—taste, aroma, and thermal sensations—and their interaction with taste and olfactory receptors. PungentDB bridges ancient wisdom and culinary innovation, offering a nuanced exploration of pungent flavors' role in enhancing food quality, safety, and sensory experiences. This initiative propels flavor chemistry forward, serving as a pivotal resource for food science advancement and the innovative application of pungent flavors.

Capsaicin: Emerging Pharmacological and Therapeutic Insights.

Capsaicin, the most prominent pungent compound of chilli peppers, has been used in traditional medicine systems for centuries; it already has a number of established clinical and industrial applications. Capsaicin is known to act through the TRPV1 receptor, which exists in various tissues; capsaicin is hepatically metabolised, having a half-life correlated with the method of application. Research on various applications of capsaicin in different formulations is still ongoing. Thus, local capsaicin applications have a pronounced anti-inflammatory effect, while systemic applications have a multitude of different effects because their increased lipophilic character ensures their augmented bioavailability. Furthermore, various teams have documented capsaicin's anti-cancer effects, proven both in vivo and in vitro designs. A notable constraint in the therapeutic effects of capsaicin is its increased toxicity, especially in sensitive tissues. Regarding the traditional applications of capsaicin, apart from all the effects recorded as medicinal effects, the application of capsaicin in acupuncture points has been demonstrated to be effective and the combination of acupuncture and capsaicin warrants further research. Finally, capsaicin has demonstrated antimicrobial effects, which can supplement its anti-inflammatory and anti-carcinogenic actions.

Cutaneous Application of Capsaicin Cream Reduces Clinical Signs of Experimental Colitis and Repairs Intestinal Barrier Integrity by Modulating the Gut Microbiota and Tight Junction Proteins.

Capsaicin, a pungent compound in chili peppers, is described as having potent anti-inflammatory, antioxidant, and antimicrobial properties. It is also described as a potential modulator of the immune system and intestinal microbiota. Oral or rectal administration of capsaicin has been studied to treat or prevent colitis. However, those vias are often not well accepted due to the burning sensation that capsaicin can cause. Our objective was to evaluate whether the application of capsaicin skin creams (0.075%) would be effective in improving inflammation and epithelial barrier function as well as the composition of the gut microbiota in a model of mild colitis induced by dextran sulfate sodium (1.5%). The results showed that the cutaneous application of capsaicin reversed weight loss and decreased colon shortening and diarrhea, all typical signs of colitis. There was also an improvement in the intestinal epithelial barrier, preserving proteins from tight junctions. We also evaluated the biodistribution of 99mtechnetium-radiolabeled capsaicin (99mTc-CAPS) applied to the back skin of the animals. We found significant concentrations of 99 mTc-Cap in the colon and small intestine after 2 and 4 h of administration. In addition, there was an increased expression of capsaicin receptor TRPV1 in the colon. Moreover, animals with colitis receiving cutaneous capsaicin presented a better short-chain fatty acid profile and increased levels of SIgA, suggesting increased microbiota diversity. In conclusion, our work opens avenues for further studies to better understand capsaicin's potential benefits and mechanisms in addressing colitis through cutaneous application.

Network pharmacology, molecular docking, and dynamics analyses to predict the antiviral activity of ginger constituents against coronavirus infection.

COVID-19 is a global pandemic that caused a dramatic loss of human life worldwide, leading to accelerated research for antiviral drug discovery. Herbal medicine is one of the most commonly used alternative medicine for the prevention and treatment of many conditions including respiratory system diseases. In this study, a computational pipeline was employed, including network pharmacology, molecular docking simulations, and molecular dynamics simulations, to analyze the common phytochemicals of ginger rhizomes and identify candidate constituents as viral inhibitors. Furthermore, experimental assays were performed to analyze the volatile and non-volatile compounds of ginger and to assess the antiviral activity of ginger oil and hydroalcoholic extract. Network pharmacology analysis showed that ginger compounds target human genes that are involved in related cellular processes to the viral infection. Docking analysis highlighted five pungent compounds and zingiberenol as potential inhibitors for the main protease (Mpro), spike receptor-binding domain (RBD), and human angiotensin-converting enzyme 2 (ACE2). Then, (6)-gingerdiacetate was selected for molecular dynamics (MD) simulations as it exhibited the best binding interactions and free energies over the three target proteins. Trajectories analysis of the three complexes showed that RBD and ACE2 complexes with the ligand preserved similar patterns of root mean square deviation (RMSD) and radius of gyration (Rg) values to their respective native structures. Finally, experimental validation of the ginger hydroalcoholic extract confirmed the existence of (6)-gingerdiacetate and revealed the strong antiviral activity of the hydroalcoholic extract with IC of 2.727 . Our study provides insights into the potential antiviral activity of (6)-gingerdiacetate that may enhance the host immune response and block RBD binding to ACE2, thereby, inhibiting SARS-CoV-2 infection.

Degradation and transformation mechanisms of pungent substances in huajiao (Zanthoxylum bungeanum) oil during storage: Induced by ultraviolet irradiation

The pungency of huajiao (scientifically known as Zanthoxylum bungeanum) oil (ZBO), a crucial seasoning oil, is notably influenced by storage conditions, an aspect insufficiently explored in current research. Through the use of high-performance liquid chromatography and liquid chromatography-mass spectrometry, this study systematically investigated the stability of pungent compounds in ZBO under various storage conditions. It also elucidated the degradation and transformation mechanisms of these substances when exposed to ultraviolet (UV) irradiation. The results underscore elevated temperature, light exposure, oxygen, and storage duration as pivotal factors influencing compound degradation, with UV light emerging as the primary driving force. After 48 h of UV exposure, the primary pungent compound, hydroxy-α-sanshool, experienced a significant loss of 85.49%, indicating a pronounced inclination towards isomerization and oxidation. Notably, this study reveals, for the first time, the possible degradation-transformation pattern of hydroxy-γ-sanshool: a mutual conversion with hydroxy-γ-isosanshool and isomerization to (2E,4E,8Z,10E,12Z)-N-(2-hydroxy-2-methylpropyl) tetradeca-2,4,8,10,12-pentaenamide.

Transient Receptor Potential Channels in the Healthy and Diseased Blood-Brain Barrier.

The large family of transient receptor potential (TRP) channels are integral membrane proteins that function as environmental sensors and act as ion channels after activation by mechanical (touch), physical (heat, pain), and chemical stimuli (pungent compounds such as capsaicin). Most TRP channels are localized in the plasma membrane of cells but some of them are localized in membranes of organelles and function as intracellular Ca2+-ion channels. TRP channels are involved in neurological disorders but their precise role(s) and relevance in these disorders are not clear. Endothelial cells of the blood-brain barrier (BBB) express TRP channels such as TRP vanilloid 1-4 and are involved in thermal detection by regulating BBB permeability. In neurological disorders, TRP channels in the BBB are responsible for edema formation in the brain. Therefore, drug design to modulate locally activity of TRP channels in the BBB is a hot topic. Today, the application of TRP channel antagonists against neurological disorders is still limited.

Transient receptor potential cation channel subfamily V member 1 (TRPV1) targeted PET imaging.

Transient receptor potential cation channel subfamily V member 1 (TRPV1) was identified using capsaicin, a pungent compound that is present in red pepper. The activation of TRPV1 induces an influx of calcium ions into cells and causes excitation of sensory neurons, associating with thermal sensing, sweating and pain. TRPV1 is also identified in various types of cancer cells. The expression of TRPV1 in cancer cells depends on the type of cancer and the stage of the disease. Therefore, TRPV1 has been considered a potential target of medicinal chemistry for drug development, and blocking its activation may lead to cancer therapy and pain relief. However, the details of the pathophysiological function of TRPV1 in vivo are still unclear. To explore practical use of TRPV1, we focused on positron emission tomography imaging and developed a 11C-radiolabeled tracer to visualize TRPV1.

The role of abiotic and biotic factors of aged brine in directing microbial assembly and volatile profiles of Paocai during fermentation

Aged brine is a representative natural starter that evolves with stable abiotic and biotic conditions for reproducible quality of fermented vegetables. In this study, the role of aged brine in directing the quality formation of Paocai (a traditional fermented vegetable) was investigated by analyzing the contribution of abiotic and biotic factors to physicochemical properties, volatile compound profiles, microbial composition and function in Paocai. Results showed that the abiotic factors in aged brine promoted reducing sugar consumption and lactic acid accumulation by facilitating the growth of indigenous lactic acid bacteria (LAB) and yeasts. Also, the masking effect of abiotic factors on isothiocyanates and disulfide alleviated the pungent flavor of Paocai. The biotic factors introduced indigenous dominant LAB genera of Liquorilactobacillus, Levilactobacillus, Lactiplantibacillus, Secundilactobacillus, Pediococcus, Lentilactobacillus, Lacticaseibacillus, Lactobacillus and indigenous dominant yeast genera of Kazachstania and Brettanomyces into Paocai. LAB functioned in the production of acid and aldehyde, while yeasts contributed to the accumulation of esters and lactones. Both LAB and yeasts reduced the contents of pungent compounds in Paocai during fermentation. Analysis of microbial function revealed that the role of aged brine was related to the regulation of carbohydrate metabolism and carbohydrate-active enzymes of the microbial community. This study provided an understanding of the role of aged brine in shaping the quality of fermented vegetables.

Dietary supplementation with capsaicinoids alleviates obesity in mice fed a high-fat-high-fructose diet.

Capsaicinoids are the pungent compounds in chili peppers. The present study investigated the effect of capsaicinoids on obesity in mice induced by a high-fat-high-fructose diet. Thirty-two male C57BL/6J mice were randomly divided into four groups (n = 8) and fed one of the following diets, namely, a low-fat diet (LFD), a high-fat-high-fructose diet (HFF), an HFF + 0.015% capsaicinoids (LCP), and an HFF + 0.045% capsaicinoids (HCP), for 12 weeks. Results showed that capsaicinoids significantly reversed HFF-induced obesity. Supplementation with capsaicinoids improved glucose tolerance, reduced plasma lipids, and attenuated inflammation. Capsaicinoids also reduced hepatic lipid accumulation by upregulating the expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α). In addition, capsaicinoids enhanced the production of fecal short-chain fatty acids (SCFAs) and increased the fecal excretion of lipids. Gut microbiota analysis revealed that capsaicinoids decreased the Firmicutes/Bacteroidetes ratio and beneficially reconstructed the microbial community. However, the effects of capsaicinoids on intestinal villus length and lipid tolerance were negligible. In conclusion, capsaicinoids effectively attenuated HFF-induced obesity and metabolic syndrome by favorably modulating lipid metabolism, improving SCFA production, and reshaping gut microbial structure.

Capsaicin orchestrates metastasis in gastric cancer via modulating expression of TRPV1 channels and driving gut microbiota disorder

The association between capsaicin, the major natural pungent compound of chili peppers, and gastric cancer progression has engendered conflicting findings. In this work, we sought to explore the character of a high capsaicin diet in gastric cancer metastasis and its possible mechanism. The impact of high capsaicin consumption on gastric cancer metastasis was investigated in vivo (xenograft mouse and zebrafish models) and in vitro (biochemical and molecular assays). It was demonstrated that high diet of capsaicin gave rise to accelerate tumor metastasis, which was partially mediated by elevating the expression of transient receptor potential vanilloid 1 (TRPV1) in gastric cancer cells. Importantly, we found that genetic depletion of TRPV1 could reduce gastric cancer metastasis by diminishing the motility of tumor cells in vitro, but acted poorly in xenograft mouse model. Considering the distribution of capsaicin in vivo, 16S rRNA sequencing and fecal microbiota transplantation (FMT) were used to appraise whether the gut microbiota involved in the high capsaicin diet induced metastasis. It was demonstrated that the level of Firmicutes and Clostridiales was expressively boosted following the high consumption of capsaicin. This microbial shift contributed to the increased peripheral 5-hydroxytryptamine (5-HT) levels, yielding the aggravated metastatic burden. Collectively, our findings highlighted the potential risk of high capsaicin diet in promoting gastric cancer metastasis by virtue of modulating TRPV1 expression and gut microbiota composition, indicating the importance of controlled consumption of chili peppers for patients with gastric cancer.CLQ_5di4C7NjAvrz19eKZiVideo

Efficacy of green solvents in pungent, aroma, and color extractions of spice oleoresins and impact on phytochemical and antioxidant capacities

The current study investigated the effect of green solvents (ethanol, acetone, and their mixture) on oleoresin yield, extraction of pungent compounds, volatiles, colorants, and the correlations with phytochemical and antioxidant activities of 5 spices (chili, black pepper, turmeric, ginger, and coriander). The solvents’ polarities and boiling points determined the oleoresin extractability, and the solvent mixture recorded the maximum yield in all spices. A total of 33 volatiles and 8 non-volatile compounds were identified in the essential oil and oleoresin fractions. Curcumin and 6-gingerol contributed to strong antioxidant properties with Pearson correlations of 0.999 and 0.924, respectively. Acetone reported the highest yield of curcumin (244.09 ± 1.71 mg/g) and 6-gingerol (131.98 ± 2.86 mg/g), whereas ethanol was the most effective solvent for capsaicinoids and piperine. Chili oleoresin extracted by ethanol delivered the maximum pungency. Acetone displayed the highest extractability of linalool detected in coriander oleoresin and essential oil. Chili oleoresin contained the highest carotenoid yield, and acetone extracted the maximum red and yellow fractions. Chili and black pepper possessed high Browning Indices and positively correlated with the total flavonoid content. β-caryophyllene dominated the essential oil profile of chili and black pepper, and the solvent mixture reported the maximum yields as 47.43% ± 0.69% and 75.11% ± 0.64%, respectively. Conclusively, the solvent mixture extracted the maximum oleoresin yield; acetone showed the highest affinity for colorants, volatiles, and antioxidants in turmeric, ginger, and coriander, while ethanol was the most efficient solvent in extracting bioactive compounds of chili and black pepper.

A basic study of pretreatment method using antibody modified with glucose oxidase for pungent‐taste measurement of taste sensor

AbstractA polyclonal antibody against the analog of piperine, which is a typical pungent taste substance, was produced, and its binding ability to piperine was evaluated using a surface plasmon resonance sensor. The antibody was labeled with glucose oxidase (GOx), and the hydrogen ions produced by the enzymatic reaction were measured at a lipid polymer membrane electrode for sourness in a taste sensor. The results showed that piperine could be detected by that polyclonal antibody; the response of the sourness sensor increased in dependence on the GOx‐labeled antibody concentration when the GOx of GOx‐labeled antibody was reacted with glucose. Thus, it was shown that uncharged pungent compounds can be converted into hydrogen ions. Pungent taste can be measured by the taste sensor using GOx‐labeled antibodies, and GOx‐labeled antibodies can be used as a pretreatment.

Optimization of an Ultrasound-Assisted Extraction Method for the Extraction of Gingerols and Shogaols from Ginger (Zingiber officinale)

The goal of this study is to optimize a UAE method for the extraction of the main bioactive compounds present in the ginger rhizome (gingerols and shogaols). Ginger rhizome (Zingiber officinale) has a considerable content of bioactive compounds, in particular gingerols and shogaols, with interesting pharmacological activities such as anti-inflammatory, antioxidant, anti-cancer, and antimicrobial properties, among others. The isolation of these compounds requires an efficient extraction process with short extraction times and the employment of specific non-toxic solvents for humans. In this work, the optimization of an ultrasound-assisted extraction (UAE) method for the extraction of the main pungent compounds in the ginger rhizome, i.e., gingerols and shogaols, has been carried out. For this purpose, a Box–Behnken design (BBD) has been used to optimize the experimental design through a response surface methodology (RSM). The percentage of ethanol in the extraction solvent, the temperature, the amplitude, and the cycle of the ultrasounds, as well as the sample-to-solvent ratio, were the variables to be studied. Thus, the percentage of ethanol in the extraction solvent was identified as the most influential factor. Once the compounds were extracted, the identification of gingerols and shogaols was performed by ultra-high-performance liquid chromatography (UHPLC) coupled to a quadrupole-time-of-flight mass spectrometer (Q-ToF-MS), and the quantification by UHPLC coupled to a diode array detector (DAD) detector. Finally, the optimized UAE method required only 10 min of extraction time, presenting good repeatability and intermediate precision levels (<5%). The method was applied to extract gingerols and shogaols from diverse sources, thereby demonstrating its applicability and highlighting the potential variations in compound concentrations across different samples based on factors such as origin, and growing conditions, among others.

The regulation of TRPA1 expression and function by Th1 and Th2-type inflammation in human A549 lung epithelial cells

BackgroundTransient Receptor Potential Ankyrin 1 (TRPA1) is a cation channel that mediates pain, itch, cough, and neurogenic inflammation in response to pungent compounds such as acrolein in cigarette smoke. TRPA1 is also activated by endogenous factors and promotes inflammation in asthma models. We have recently shown that TRPA1 is upregulated by inflammatory cytokines in A549 human lung epithelial cells. Here, we explored the effects of Th1 and Th2-type inflammation on TRPA1.Methods and resultsTRPA1 expression and function was studied in A549 human lung epithelial cells. To induce inflammation, the cells were exposed to a combination of cytokines TNF-α and IL-1β; and to model Th1 or Th2-type responses, IFN-γ or IL-4/IL-13 was added, respectively. TRPA1 expression (measured by RT-PCR and Western blot) and function (assessed by Fluo-3AM intracellular calcium measurement) was enhanced under the influence of TNF-α + IL-1β. IFN-γ further enhanced TRPA1 expression and function, whereas IL-4 and IL-13 suppressed them. The effects of IFN-γ and IL-4 on TRPA1 expression were reversed by the Janus kinase (JAK) inhibitors baricitinib and tofacitinib, and those of IL-4 also by the STAT6 inhibitor AS1517499. The glucocorticoid dexamethasone downregulated TRPA1 expression, whereas the PDE4 inhibitor rolipram had no effect. Under all conditions, TRPA1 blockade was found to reduce the production of LCN2 and CXCL6.ConclusionsTRPA1 expression and function in lung epithelial cells was upregulated under inflammatory conditions. IFN-γ further increased TRPA1 expression while IL-4 and IL-13 suppressed that in a JAK-STAT6 dependent manner which is novel. TRPA1 also modulated the expression of genes relevant to innate immunity and lung disease. We propose that the paradigm of Th1 and Th2 inflammation is a major determinant of TRPA1 expression and function, which should be considered when targeting TRPA1 for pharmacotherapy in inflammatory (lung) disease.

DESCRIBING THE GINGER PLANT AND ITS EFFECTIVE INGREDIENTS ALONG WITH ITS THERAPEUTIC PROPERTIES IN VARIOUS COMPLICATIONS

Abstract Plants are one of the important and valuable sources in the preparation of medicines, both in traditional medicine and in the form of pure products. Ginger is obtained from a yellow plant with purple veins with the scientific name Zingiber officinale. Although ginger is usually referred to as the root of the plant, actually the part used is the swollen underground stem called the rhizome. The aroma and flavor of ginger are due to the presence of two types of volatile oils and non-volatile pungent compounds. The biologically active components of ginger are classified in the second category, among the most important molecules in this category, are gingerol and shogaol, which cause a pungent sensation in the mouth. Most properties of ginger are attributed to non-volatile components with a spicy taste. The properties of these substances can be reduced blood sugar, weight loss, increased blood insulin, effect on blood coagulation, effect on blood pressure, reduction of complications of gastrointestinal diseases, reduction of nausea caused by pregnancy, or the use of chemotherapy drugs, the protective effect of the tissue against chemical and radio damage with anti-inflammatory properties, antioxidant properties, antibacterial and antifungal properties, especially Candida albicans, anti-cancer properties through antioxidant and anti-inflammatory properties. This study aimed to describe the ginger plant and its active ingredients and some features including anti-inflammatory effects, anti-oxidative effects, anti-cancer effects, and so on.

味覚センサの辛味測定のためのグルコース酸化酵素標識抗体を用いた前処理法の基礎検討

A polyclonal antibody against the analog of piperine, which is a typical pungent taste substance, was produced, and its binding ability to piperine was evaluated using a surface plasmon resonance sensor. The antibody was labeled with glucose oxidase (GOx), and the hydrogen ions produced by the enzymatic reaction were measured at a lipid polymer membrane electrode for sourness in a taste sensor. The results showed that piperine could be detected by that polyclonal antibody; the response of the sourness sensor increased in dependence on the GOx-labeled antibody concentration when the GOx of GOx-labeled antibody was reacted with glucose. Thus, it was shown that uncharged pungent compounds can be converted into hydrogen ions. Pungent taste can be measured by the taste sensor using GOx-labeled antibodies, and GOx-labeled antibodies can be used as a pretreatment.

Quality Improvement of Garlic Paste by Whey Protein Isolate Combined with High Hydrostatic Pressure Treatment

Garlic, one of the most popular spices and medical herbs, has a unique pungent flavor and taste. Conventional homogenization and thermal treatment commonly lead to flavor and color deterioration in garlic paste, because allicin is highly susceptible to degradation and reaction. The present study was to investigate the effects of whey protein isolate (WPI) and different levels of high hydrostatic pressure (HHP, 200, 300, 400, 500, and 600 MPa) on the quality of garlic paste. Results showed that the addition of WPI in the homogenization of garlic significantly prevented green discoloration. Furthermore, WPI plus HHP under 500 MPa could better protect the color of garlic paste. Higher pressure (600 MPa) led to WPI aggregation, resulting in higher green color chroma of garlic paste. GC-MS results revealed that the application of WPI and HHP in garlic paste increased the relative level of pungent flavor compounds and decreased those of unpleasant odor compounds. The correlation analysis results revealed that WPI efficiently prevented garlic green discoloration, which is attributed to the thiol group in WPI exchanging the sulfonyl groups in allicin. In consideration of the microbial load, flavor and color quality of garlic paste, the optimal processing conditions were found at 500 MPa for 5 min with 2% WPI addition, extending shelf life to 25 days.

Reusable Electronic Tongue Based on Transient Receptor Potential Vanilloid 1 Nanodisc-Conjugated Graphene Field-Effect Transistor for a Spiciness-Related Pain Evaluation.

The sense of spiciness is related to the stimulation of vanilloid compounds contained in the foods. Although, the spiciness is commonly considered as the part of taste, it is more classified to the sense of pain stimulated on a tongue, namely, pungency, which is described as a tingling or burning on the tongue. Herein, first, a reusable electronic tongue based on a transient receptor potential vanilloid 1 (TRPV1) nanodisc conjugated graphene field-effect transistor is fabricated and spiciness-related pain evaluation with reusable electrode is demonstrated. The pungent compound reactive receptor TRPV1 is synthesized in the form of nanodiscs to maintain stability and reusability. The newly developed platform shows highly selective and sensitive performance toward each spiciness related vanilloid compound repeatably: 1 aM capsaicin, 10 aM dihydrocapsaicin, 1 fM piperine, 10nM allicin, and 1 pM AITC. The binding mechanism is also examined by simulation. Furthermore, the elimination of the burning sensation on the tongue after eating spicy foods is not investigated. Based on the synthesis of micelles composed of casein protein (which is contained in skim milk) that remove pungent compounds bound to TRPV1 nanodisc, the deactivation of TRPV1 is investigated, and the electrode is reusable that mimics electronic tongue.

Cost-Effective Pipeline for a Rational Design and Selection of Capsaicin Analogues Targeting TRPV1 Channels.

Transient receptor potential (TRP) channels constitute a large group of membrane receptors associated with sensory pathways in vertebrates. One of the most studied is TRPV1, a polymodal receptor tuned for detecting heat and pungent compounds. Specific inhibition of the nociceptive transduction at the peripheral nerve represents a convenient approach to pain relief. While acting as a chemoreceptor, TRPV1 shows high sensitivity and selectivity for capsaicin. In contrast to the drugs available on the market that target the inflammatory system, TRPV1 antagonists act as negative modulators of nociceptive transduction. Therefore, the development of compounds modulating TRPV1 activity has expanded dramatically over time. Experimental data suggest that most agonist and antagonist drugs interact at or near capsaicin's binding site. In particular, the properties of capsaicin's head play an essential role in modulating potency and affinity. Here, we explored a cost-efficient pipeline to predict the effects of introducing chemical modifications into capsaicin's head region. An extensive set of molecules was selected by first considering the geometrical properties of capsaicin's binding site and then molecular docking. Finally, the novel ligands were ranked by combining molecular and pharmacokinetic predictions.

Capsicum Waste as a Sustainable Source of Capsaicinoids for Metabolic Diseases

Capsaicinoids are pungent alkaloid compounds enriched with antioxidants, anti-microbial, anti-inflammatory, analgesics, anti-carcinogenic, anti-obesity and anti-diabetic properties. These compounds are primarily synthesised in the placenta of the fruit and then transported to other vegetative parts. Different varieties of capsicum and chillies contain different capsaicinoid concentrations. As capsicums and chillies are grown extensively throughout the world, their agricultural and horticultural production leads to significant amount of waste generation, in the form of fruits and plant biomass. Fruit wastes (placenta, seeds and unused fruits) and plant biowaste (stems and leaves) can serve as sources of capsaicinoids which can provide opportunities to extract these compounds for development of nutraceutical products using conventional or advanced extraction techniques. Capsaicin and dihydrocapsaicin are two most abundantly found pungent compounds. Considering the health benefits of capsaicinoids, these compounds can help in reducing metabolic disease complications. The development of an advanced encapsulation therapy of safe and clinically effective oral capsaicinoid/capsaicin formulation seem to require evaluation of strategies to address challenges related to the dosage, limited half-life and bioavailability, adverse effects and pungency, and the impacts of other ligands antagonising the major capsaicinoid receptor.