Role of Aromatic Herbs and Spices in Salty Perception of Patients with Hyposmia.

Herbs and spices represent a possibility for the improvement of anosmia and ageusia. In this work we evaluated the role of Mediterranean aromatic herbs and spices in the salty taste perception of patients with hyposmia compared to healthy controls. To this goal, the salty taste perception in response to pure salt and different types of commercial flavored sea salt was assessed in patients with hyposmia, with or without a post-acute coronavirus syndrome, and healthy controls. Myrtle berries and leaves, a mixture of Mediterranean herbs and plants such as helichrysum, rosemary, liquorice, fennel seeds and myrtle leaves, oranges and saffron were used as salt flavoring ingredients. Differences in gustatory perception between 57 patients with hyposmia and 91 controls were evaluated considering the rate of the gustatory dimensions of pleasantness, intensity, and familiarity, using a 7-point hedonic Likert-type scale. At a dose of 0.04 g/mL, saline solutions of flavored salts, with an average 15% less NaCl, were perceived by patients with hyposmia as equally intense but less familiar than pure salt solution, with similar scores in the pleasantness dimension. Our study highlighted the central role of Mediterranean aromatic plants in the enhancement of salty perception in patients with hyposmia.

Ayurveda and COVID-19: Where psychoneuroimmunology and the meaning response meet.

The COVID-19 pandemic has led to high levels of psychological distress in the general public, including symptoms of anxiety and depression. Such distress is associated with alterations in immune function, including an elevated risk of viral respiratory tract infections. In this light, the possible effects of Ayurveda, a traditional system of medicine promoted by the Indian government as an "immune booster", are examined from the point of view of psychoneuroimmune mechanisms as well as the "meaning response" described by Moerman. It was found that many of the measures advocated in their guidelines could positively influence immunity either by direct effects on symptoms of depression or anxiety, or through their symbolic significance. Therefore, it is possible that such traditional practices could be beneficial both in terms of psychological quality of life, and in terms of moderating the risk of infection.

Indian spices: past, present and future challenges as the engine for bio-enhancement of drugs: impact of COVID-19.

Spices are natural plant products enriched with the history of being used as herbal medicine for prevention of diseases. India is also known as the 'Land of Spices'. Out of 109 spices recognized by the International Organization for Standardization (ISO) more than 52-60 spice crops are grown in India. The major spices exported by India are turmeric, cumin, coriander, fenugreek, peppers, etc. The Indian spices are divided into three era viz. early period, middle age and early modern period. Spices are used in beverages, liquors, and pharmaceutical, cosmetic and perfumery products. The major issue with spices is their handling and storage. This review article mainly focuses on two aspects: at the outset the handling and storage of the spices is an essential factor as spices are available in different forms like raw, processed, fresh, whole dried, or pre-ground dried. Therefore, the need of processing, packaging, storage and handling of the spices is important as the deterioration of spices can lead to the loss of therapeutic activity. Furthermore, many herbal constituents have the capability to enhance the bioavailability of drugs. Therefore, an attempt has been made to throw a light on the bioenhancer activity and therapeutic activity along with their mechanism of action of some Indian spices which are regularly used for cooking purpose on a daily basis to enhance the taste of food. The spices suggested by ministry of AYUSH which is relevant to its medicinal and biological property in treatment and prevention from COVID-19 are discussed. © 2022 Society of Chemical Industry.

COVID-19, cytokines, inflammation, and spices: How are they related?

BACKGROUND: Cytokine storm is the exaggerated immune response often observed in viral infections. It is also intimately linked with the progression of COVID-19 disease as well as associated complications and mortality. Therefore, targeting the cytokine storm might help in reducing COVID-19-associated health complications. The number of COVID-19 associated deaths (as of January 15, 2021; https://www.worldometers.info/coronavirus/) in the USA is high (1199/million) as compared to countries like India (110/million). Although the reason behind this is not clear, spices may have some role in explaining this difference. Spices and herbs are used in different traditional medicines, especially in countries such as India to treat various chronic diseases due to their potent antioxidant and anti-inflammatory properties. AIM: To evaluate the literature available on the anti-inflammatory properties of spices which might prove beneficial in the prevention and treatment of COVID-19 associated cytokine storm. METHOD: A detailed literature search has been conducted on PubMed for collecting information pertaining to the COVID-19; the history, origin, key structural features, and mechanism of infection of SARS-CoV-2; the repurposed drugs in use for the management of COVID-19, and the anti-inflammatory role of spices to combat COVID-19 associated cytokine storm. KEY FINDINGS: The literature search resulted in numerous in vitro, in vivo and clinical trials that have reported the potency of spices to exert anti-inflammatory effects by regulating crucial molecular targets for inflammation. SIGNIFICANCE: As spices are derived from Mother Nature and are inexpensive, they are relatively safer to consume. Therefore, their anti-inflammatory property can be exploited to combat the cytokine storm in COVID-19 patients. This review thus focuses on the current knowledge on the role of spices for the treatment of COVID-19 through suppression of inflammation-linked cytokine storm.

Eugenol, a Component of Holy Basil (Tulsi) and Common Spice Clove, Inhibits the Interaction Between SARS-CoV-2 Spike S1 and ACE2 to Induce Therapeutic Responses.

Spike S1 of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) on host cells to enter the cell and initiate COVID-19. Since ACE2 is a favorable enzyme, we were interested in finding a molecule capable of binding spike S1, but not ACE2, and inhibiting the interaction between spike S1 and ACE2. Holy basil (Tulsi) has a long history as a medicine for different human disorders. Therefore, we screened different components of Tulsi leaf and found that eugenol, but not other major components (e.g. ursolic acid, oleanolic acid and ß-caryophylline), inhibited the interaction between spike S1 and ACE2 in an AlphaScreen-based assay. By in silico analysis and thermal shift assay, we also observed that eugenol associated with spike S1, but not ACE2. Accordingly, eugenol strongly suppressed the entry of pseudotyped SARS-CoV-2, but not vesicular stomatitis virus (VSV), into human ACE2-expressing HEK293 cells. Eugenol also reduced SARS-CoV-2 spike S1-induced activation of NF-κB and the expression of IL-6, IL-1ß and TNFα in human A549 lung cells. Moreover, oral treatment with eugenol reduced lung inflammation, decreased fever, improved heart function, and enhanced locomotor activities in SARS-CoV-2 spike S1-intoxicated mice. Therefore, selective targeting of SARS-CoV-2 spike S1, but not ACE2, by eugenol may be beneficial for COVID-19 treatment.

Spices and herbs: Potential antiviral preventives and immunity boosters during COVID-19.

A severe acute respiratory syndrome is an unusual type of contagious pneumonia that is caused by SARS coronavirus. At present, the whole world is trying to combat this coronavirus disease and scientific communities are putting rigorous efforts to develop vaccines. However, there are only a few specific medical treatments for SARS-CoV-2. Apart from other public health measures taken to prevent this virus, we can boost our immunity with natural products. In this article, we have highlighted the potential of common spices and herbs as antiviral agents and immunity boosters. A questionnaire-based online survey has been conducted on home remedies during COVID-19 among a wide range of peoples (n-531) of different age groups (13-68 years) from various countries. According to the survey, 71.8% of people are taking kadha for combating infection and boosting immunity. Most people (86.1%) think that there is no side effect of kadha while 13.9% think vice versa. A total of 93.6% of people think that spices are helpful in curing coronavirus or other viral infection as well as boosting immunity. Most people are using tulsi drops, vitamin C, and chyawanprash for boosting their immunity. Therefore, we conclude from the survey and available literature that spices and herbs play a significant role against viral infections.

Trachyspermum ammi and Cinnamomum verum as nutraceuticals: Spices rich in therapeutically significant protein tyrosine phosphatases.

Nutraceuticals need special attention as preventive molecules to create a natural barrier against various dreadful diseases like cancer and to regulate metabolism. In the present study, two spices, Trachyspermum ammi and Cinnamomum verum, been identified as excellent Protein Tyrosine Phosphatases (PTPases) sources that play significant role in the regulation of cell signal transduction and developmental processes in plants as well as animals, being lucrative and potential targets for pharmacological modulation. PTPases from both cases were partially purified into 0%-40% and 40%-80% fractions based on ammonium sulfate saturation levels. Fraction (40%-80%) exhibited a purification level of 4.44-fold and 2.86-fold with specific activity of 44.06 and 23.33 U/mg for PTPases from T. ammi and C. verum, respectively. PTPases being found to be thermally stable up to 70°C imply their industrial significance. Kinetic studies showed Km values to be 7.14 and 8.33 mM, whereas the activation energy (Ea ) values were 25.89 and 29.13 kJ/mol, respectively. Divalent cations: Cu2+ , Zn2+ , and Mn2+ acted as inhibitors of PTPases, from both sources. The Ki values of inhibitors varied from 0.014-0.125 mM in the descending order Cu2+  > Zn2+  > Mn2+ and Mn2+  > Cu2+  > Zn2+ for PTPases from T. ammi and C. verum, respectively. The inhibitory effect of sodium metavanadate aligns with prominent PTPase characteristics. In addition to these properties, the thermostability of PTPases from two spices enhances their significance in industries with therapeutically vital products. Although the source of PTPases is culinary spices, further studies are required to establish the utilization of PTPases as nutraceuticals and in therapeutic formulations. PRACTICAL APPLICATIONS: For a healthy lifestyle, awareness needs to be created by humankind towards food habits to minimize illnesses. Numerous studies have explored the consumption of nutraceutical products acts as a natural barrier and immune booster for various human ailments including SARS-COV-2. PTPases play important roles in regulating intracellular signaling and, ultimately, biological function along with their structural features. The importance of PTPases and their inhibitors has been implicated in various diseases like cancer, diabetes, and obesity. Further investigations need to be undertaken to explore the therapeutic properties of PTPases in both in vivo and in vitro for their clinical significance.

Unravelling the Immune Modulatory Effect of Indian Spices to Impede the Transmission of COVID-19: A Promising Approach.

Months after WHO declared COVID-19 as a Global Public Health Emergency of International Concern, it does not seem to be flattening the curve as we are still devoid of an effective treatment modality and vaccination is in the first phase in many countries. Amid such uncertainty, being immune is the best strategy to defend against corona attacks. As the whole world is referring back to immune-boosting traditional remedies, interest is rekindled in the Indian system of Medicine, which is gifted with an abundance of herbal medicines as well as remedies. Among them, spices (root, rhizome, seed, fruit, leaf, bud, and flower of various plants used to add taste and flavors to food) are bestowed with immense medicinal potential. A plethora of clinical as well as preclinical studies reported the effectiveness of various spices for various ailments. The potential immune-boosting properties together with their excellent safety profiles are making spices the current choice of phytoresearch as well as the immune-boosting home remedies during these sceptical times. The present review critically evaluates the immune impact of various Indian spices and their potential to tackle the novel coronavirus, with comments on the safety and toxicity aspects of spices.

In Silico Studies Reveal Antiviral Effects of Traditional Indian Spices on COVID-19.

BACKGROUND: The global health emergency due to SARS-CoV-2 causing the COVID-19 pandemic emphasized the scientific community to intensify their research work for its therapeutic solution. In this study, Indian traditional spices owing to various medicinal properties were tested in silico for their inhibitory activity against SARS-CoV-2 proteins. SARS-CoV-2 spike proteins (SP) and main proteases (Mpro) play a significant role in infection development were considered as potential drug targets. METHODS: A total of 75 phytochemicals present in traditional Indian spices retrieved from the published literature and Dr. Duke's Phytochemical and Ethnobotanical Database, were docked with Mpro (PDB IDs: 6YNQ), and the SP (PDB IDs: 6LXT and 6YOR). RESULTS: Through the screening process, 75 retrieved phytochemicals were docked with spike protein (PDB IDs: 6LXT and 6YOR) and main protease (PDB ID: 6YNQ) of SARS-CoV-2. Among them, myricetin, a flavonoid (rank score: 6LXT: -11.72383; 6YOR: -9.87943; 6YNQ: -11.68164) from Allium sativum L and Isovitexin, an example of flavone (rank score: 6LXT: -12.14922; 6YOR: -10.19443; 6YNQ: -12.60603) from Pimpinella anisumL were the most potent ligands against SP and Mpro of SARS-CoV-2. Whereas, Astragalin from Crocus sativus L.; Rutin from Illicium verum, Oxyguttiferone from Garcinia cambogia; Scopolin from Apium graveolens L, Luteolin from Salvia officinalis, Emodin, Aloe-emodin from Cinnamomum zeylanicium and Apigenin from Allium sativum L showed better inhibition against Mpro than SP of SARS-CoV-2. The amino acid residues like SER, LYS, ASP and TYR were found playing important role in protein-ligand interactions via hydrogen bonding and Vander Waals forces. CONCLUSION: Optimal use of traditional spices in our daily meals may help fight against COVID-19. This study also paves the path for herbal drug formulation against SARS-CoV-2 after wet lab validation.

Spices to Control COVID-19 Symptoms: Yes, but Not Only .

There are large country variations in COVID-19 death rates that may be partly explained by diet. Many countries with low COVID-19 death rates have a common feature of eating large quantities of fermented vegetables such as cabbage and, in some continents, various spices. Fermented vegetables and spices are agonists of the antioxidant transcription factor nuclear factor (erythroid-derived 2)-like 2 (Nrf2), and spices are transient receptor potential ankyrin 1 and vanillin 1 (TRPA1/V1) agonists. These mechanisms may explain many COVID-19 symptoms and severity. It appears that there is a synergy between Nrf2 and TRPA1/V1 foods that may explain the role of diet in COVID-19. One of the mechanisms of COVID-19 appears to be an oxygen species (ROS)-mediated process in synergy with TRP channels, modulated by Nrf2 pathways. Spicy foods are likely to desensitize TRP channels and act in synergy with exogenous antioxidants that activate the Nrf2 pathway.

Culinary spice bioactives as potential therapeutics against SARS-CoV-2: Computational investigation.

BACKGROUND: Coronavirus disease-2019 (COVID-19) is an infectious pandemic caused by SARS-CoV-2. SARS-CoV-2 main protease (Mpro) and spike protein are crucial for viral replication and transmission. Spike protein recognizes the human ACE2 receptor and transmits SARS-CoV-2 into the human body. Thus, Mpro, spike protein, and ACE2 receptor act as appropriate targets for the development of therapeutics against SARS-CoV-2. Spices are traditionally known to have anti-viral and immune-boosting activities. Therefore, we investigated the possible use of selected spice bioactives against the potential targets of SARS-CoV-2 using computational analysis. METHODS: Molecular docking analysis was performed to analyze the binding efficiency of spice bioactives against SARS-CoV-2 target proteins along with the standard drugs. Drug-likeness properties of selected spice bioactives were investigated using Lipinski's rule of five and the SWISSADME database. Pharmacological properties such as ADME/T, biological functions, and toxicity were analyzed using ADMETlab, PASS-prediction, and ProTox-II servers, respectively. RESULTS: Out of forty-six spice bioactives screened, six bioactives have shown relatively better binding energies than the standard drugs and have a higher binding affinity with at least more than two targets of SARS-CoV-2. The selected bioactives were analyzed for their binding similarities with the standard drug, remdesivir, towards the targets of SARS-CoV-2. Selected spice bioactives have shown potential drug-likeness properties, with higher GI absorption rate, lower toxicity with pleiotropic biological roles. CONCLUSIONS: Spice bioactives have the potential to bind with the specific targets involved in SARS-CoV-2 infection and transmission. Therefore, spice-based nutraceuticals can be developed for the prevention and treatment of COVID-19.

Secondary metabolites from spice and herbs as potential multitarget inhibitors of SARS-CoV-2 proteins.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been responsible for the current global pandemic that has caused a death toll of >1.12 million worldwide and number continues to climb in several countries. Currently, there are neither specific antiviral drugs nor vaccines for the treatment and prevention of COVID-19. We screened in silico, a group of natural spice and herbal secondary metabolites (SMs) for their inhibition efficacy against multiple target proteins of SARS-CoV-2 as well as the human angiotensin-converting enzyme 2 protein. Docking and simulation results indicated that epicatechin, embelin, hesperidin, cafestol, murrayanine and murrayaquinone-A have higher inhibition efficacy over at least one of the known antiviral drugs such as Hydroxychloroquine, Remdesivir and Ribavirin. Combination of these potentially effective SMs from their respective plant sources was analysed, and its absorption and acute oral toxicity were examined in Wistar rats and classified as category 5 as per the Globally Harmonized System. The identified SMs may be useful in the development of preventive nutraceuticals, food supplements and antiviral drugs.Communicated by Ramaswamy H. Sarma.

Spice-infused palmyra palm syrup improved cell-mediated immunity in Wistar Albino rats.

Spices attract tremendous attention in the management of viral infections. However, scientific validation is vital to recommend spices as nutraceuticals or functional foods. In the present work, we have selected three spices based on Ayurvedic knowledge and developed a nutraceutical for immunomodulation. Trikatu, a blend of ginger, black pepper, and long pepper, is used in the Indian Ayurvedic system, along with many herbs, for various ailments. We formulated a "Trikatu syrup" (TS) using these three spices and palmyra palm neera. Carbon clearance assay, neutrophil adhesion test, and sheep red blood cell (SRBC)-induced delayed-type hypersensitivity (DTH) reaction was performed to investigate the immunomodulatory potential of TS in Wistar Albino rats. The rats fed with TS showed a dose-dependent increase in footpad thickness compared to control rats, suggesting cell-mediated immunity. The major bioactive piperine in TS was isolated and quantified. PRACTICAL APPLICATIONS: Spices are consumed worldwide as a flavor enhancer in food. Besides, spices have an array of bioactive molecules with a multitude of health benefits. In the backdrop of COVID-19, immunomodulation and antiviral properties of spices are discussed widely. The present study is intended to explore the potential of three selected spices (ginger, black pepper, and long pepper) beyond its application in typical food preparations. The syrup formulated in this study by using these three spices improved cell-mediated immunity in Wistar Albino rats. The study warrants further validation studies of the formulated product for providing indisputable claims for the immunomodulation properties.

Identification of potential inhibitors of SARS-CoV-2 main protease and spike receptor from 10 important spices through structure-based virtual screening and molecular dynamic study.

The outbreak of novel coronavirus disease (COVID-19) caused by SARS-CoV-2 poses a serious threat to human health and world economic activity. There is no specific drug for the treatment of COVID-19 patients at this moment. Traditionally, people have been using spices like ginger, fenugreek and onion, etc. for the remedy of a common cold. This work identifies the potential inhibitors of the main protease (Mpro) and spike (S) receptor of SARS-CoV-2 from 10 readily available spices. These two proteins, S and Mpro, play an important role during the virus entry into the host cell, and replication and transcription processes of the virus, respectively. To identify potential molecules an in-house databank containing 1040 compounds was built-up from the selected spices. Structure-based virtual screening of this databank was performed with two important SARS-CoV-2 proteins using Glide. Top hits resulted from virtual screening (VS) were subjected to molecular docking using AutoDock 4.2 and AutoDock Vina to eliminate false positives. The top six hits against Mpro and top five hits against spike receptor subjected to 130 ns molecular dynamic simulation using GROMACS. Finally, the compound 1-, 2-, 3- and 5-Mpro complexes, and compound 17-, 18-, 19-, 20- and 21- spike receptor complexes showed stability throughout the simulation time. The ADME values also supported the drug-like nature of the selected hits. These nine compounds are available in onion, garlic, ginger, peppermint, chili and fenugreek. All the spices are edible and might be used as home remedies against COVID-19 after proper biological evaluation.

In silico investigation of spice molecules as potent inhibitor of SARS-CoV-2.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel infectious disease that is in rapid growth. Several trials are going on worldwide to find a solution for this pandemic. The viral replication can be blocked by inhibiting the receptor-binding domain (RBD) of SARS-CoV-2 spike protein (SARS-CoV-2 RBD Spro) and the SARS-CoV-2 main protease (SARS-CoV-2 Mpro). The binding of potential small molecules to these proteins can inhibit the replication and transcription of the virus. The spice molecules that are used in our food have antiviral, antifungal and antimicrobial properties. As spice molecules are consumed in the diet, hence its antiviral properties against SARS-CoV-2 will benefit in a significant manner. Therefore, in this work, the molecular docking of 30 selected spice molecules (screened through ADME property) was performed to identify the potential inhibitors for the RBD Spro and Mpro of SARS-CoV-2. We have found that though all the molecules bind actively with the SARS-CoV-2 RBD Spro and Mpro, but Piperine has the highest binding affinity among the 30 screened molecules. Besides, the comparative study between Piperine and currently used drugs show that Piperine is more effective. The interaction of Piperine with RBD Spro and Mpro is further validated by the molecular dynamics (MD) simulation studies. The free energy landscape and binding free energy results also, support for the stable complex formation of Piperine with RBD Spro and Mpro. We anticipate immediate wet-lab experiments and clinical trials in support of this computational study that might help to inhibit the SARS-CoV-2 virus. Communicated by Ramaswamy H. Sarma.

Remote psychophysical evaluation of olfactory and gustatory functions in early-stage coronavirus disease 2019 patients: the Bologna experience of 300 cases.

BACKGROUND: An objective evaluation of coronavirus disease 2019 in the first days of infection is almost impossible, as affected individuals are generally in home quarantine, and there is limited accessibility for the operator who should perform the test. To overcome this limitation, a recently validated psychophysical self-administered test was used, which can be performed remotely in the assessment of early-stage coronavirus disease 2019 patients. METHODS: Olfactory and gustatory functions were objectively assessed in 300 patients in the first 7 days from coronavirus disease 2019 symptom onset. RESULTS: Seventy per cent of the patients presented olfactory and/or gustatory disorders. The dysfunctions detected were mainly complete anosmia (47 per cent) or ageusia (38 per cent). A significant correlation was found between taste dysfunction and female gender (odds ratio = 1.936, p = 0.014) and fever (odds ratio = 2.132, p = 0.003). CONCLUSION: The psychophysical evaluation protocol proposed is an effective tool for the fast and objective evaluation of patients in the early stages of coronavirus disease 2019. Chemosensitive disorders have been confirmed to be frequent and early symptoms of the coronavirus infection, and, in a significant number of cases, they are the first or only manifestation of coronavirus disease 2019.

Immunity-Boosting Spices and the Novel Coronavirus.

Although there is no reported genetic predisposition in contracting coronavirus disease 2019 (COVID-19), the mortality rate varies among different ethnic groups. Here we determined potential correlation between COVID-19 and spice consumption. The data from 163 countries including total cases, total deaths, and total recovered were analyzed. It was observed that there is a clear interrelated prevalence between the total number of COVID-19 cases per million population tested and the gram of spice supply per capita per day. Nations with lower consumptions of spices per capita showed greater number of COVID-19 cases per million population. This is not surprising as herbs and spices are well-known to boost immunity. Although the precise molecular mechanisms associated with spices and immunity are not completely understood, our findings led us to hypothesize that spice consumption plays a role in our ability to fight COVID-19; however, intensive research is needed to determine the translational value of these findings.

Pharmacological (or Synthetic) and Nutritional Agonists of PPAR-γ as Candidates for Cytokine Storm Modulation in COVID-19 Disease.

The cytokine storm is an abnormal production of inflammatory cytokines, due to the over-activation of the innate immune response. This mechanism has been recognized as a critical mediator of influenza-induced lung disease, and it could be pivotal for COVID-19 infections. Thus, an immunomodulatory approach targeting the over-production of cytokines could be proposed for viral aggressive pulmonary disease treatment. In this regard, the peroxisome proliferator-activated receptor (PPAR)-γ, a member of the PPAR transcription factor family, could represent a potential target. Beside the well-known regulatory role on lipid and glucose metabolism, PPAR-γ also represses the inflammatory process. Similarly, the PPAR-γ agonist thiazolidinediones (TZDs), like pioglitazone, are anti-inflammatory drugs with ameliorating effects on severe viral pneumonia. In addition to the pharmacological agonists, also nutritional ligands of PPAR-γ, like curcuma, lemongrass, and pomegranate, possess anti-inflammatory properties through PPAR-γ activation. Here, we review the main synthetic and nutritional PPAR-γ ligands, proposing a dual approach based on the strengthening of the immune system using pharmacological and dietary strategies as an attempt to prevent/treat cytokine storm in the case of coronavirus infection.