A review on quality control, toxicity and clinical application of Amomum tsao-ko Crevost & Lemarie

The dried fruit of Amomum tsao-ko Crevost & Lemarie, a perennial herb of Cardamom in Zingiberaceae, has been widely used in food and as a folk medicine. It is used not only as an important food additive and spice for removing peculiar smell and improving taste, but also as a traditional Chinese medicine with significant efficacy in treating many kinds of disorders. Based on the high edible and medicinal value, large amounts of investigation have been reported for A. tsaoko in the past several years. This review specifically summarises its quality control, toxicology and clinical application, about which no literature had systematically reviewed, based on our best acknowledge. The current quality control of A. tsaoko is based on the content of volatile oil, which should be no less than 1.4% according to the Pharmacopoeia of the People's Republic of China (2020 edition), while a more possible Q-Markers should be developed to focus on either a specific bioactive ingredient or a component correlated with a certain clinical efficacy. Toxicity research suggests that A. tsaoko actually belongs to the non-toxic substance, although citral and 1,8-cineole, two main components of A. tsaoko, is hepatotoxic for the former and displays low acute toxicity and sub-chronic oral toxicity for the latter, but no obviously accumulative toxicity has so far been discovered for A. tsaoko. In clinical practice, A. tsaoko is often used in treatment of dampness/cold resistance, malaria, vomiting, fullness and epigastric distension across additional disorders, such as SARS, COVID-19 and hepatitis.Copyright © 2022 The Author(s)

Extending the Record of Terpenes from Soft Coral Sarcophyton mililatensis.

In the present study, a new polyoxygenated cembranoid named sarcomililatol H (1) as well as six known terpenes 2-7 with different skeletons were isolated from South China Sea soft coral Sarcophyton mililatensis. Based on the comprehensive analyses of 1D and 2D NMR spectroscopic data, the structure of the new compound 1 was established. This new cembranoid was characterized by the presence of the rarely encountered tetrahydropyran ring with the ether linkage across C-2 and C-12. By applying the time-dependent density functional theory electronic circular dichroism (TDDFT ECD) approach, the absolute configuration of sarcomililatol H (1) was determined. All of the isolates were subjected to the anti-inflammatory and anti-tumor bioassays. However, none of them was active in these evaluations. Additionally, the preliminary virtual screening of inhibitory against SARS-CoV-2 by molecular docking showed that diterpene 1 could be regarded as a SARS-CoV-2 main protease (Mpro ) inhibitor (binding energy: -7.63 kcal/mol). The discovery of these terpenes has expanded the chemical diversity and complexity of terpenes from the species S. mililatensis.

A Review of Phytochemistry and Pharmacology on Moringa Oleifera

Natural extracts have been of very interest since ancient times due to their enormous medicinal use and research attention. Moringa oleifera is well known as miracle tree as it consists of high nutritive values. Originally from India is widely distributed in many tropical regions, in the pacific region, west Africa as well as central America. India is the major supplier of Moringa worldwide, accounting for around 80% of global demand. It is a multipurpose plant cultivated for medicinal applications. It contains rich sources of Vit- A, B1, B2, B3 and C, It also has calcium, potassium, iron, magnesium, zinc and phospherus. Moringa species contain various phytoconstituents such as alkaloids, saponins,tannins, steroids.phenolic acids( gallic, vanillic and p-coumaric acids) and flavanoids(catechin), tocopherol ,glucosinolates and terpenes. Investigations of ethanol extract of the leaves gives lutein, B-carotene,phytyl fatty acids, esters, poly phenols, B- sitosterols,triglycerols,fatty acids and saturated hydrocarbons. Leaves were obtained by super critical extraction with CO2 using ethanol as a cosolvent, temperature 35-80 0C.The phenolic acids( gallic, vanillic and p- coumaric acids) and flavanoids(catechin) were identified in all extracts. Extracts obtained at 35 degrees shows the highest values of total phenolic compounds. The activities of plant include Anti-oxidants, anti-cancer, anti-microbial, anti-viral,anti- hyperglycemic,anti-hyperlipidemic,anti-inflammatory,anti-hypertension, anti-spasmodic and others. Due to covid-19 pandemic, the global Moringa products market size is estimated to be worth USD 5167.2 million in 2022. Leaf powder is expected to exceed USD 6 billion by 2025 on account of increasing demand in the dietary supplement and food applications.

Uncovering the inhibitory potentials of Phyllanthus nivosus leaf and its bioactive compounds against Plasmodium lactate dehydrogenase for malaria therapy.

Malaria control efforts have been hampered due to the emergence of resistant malaria parasite strains and the coinciding events of Covid-19. The quest for more effective and safe treatment alternatives is driving a slew of new studies that must be accelerated if malaria can be overcome. Due to its reported antimalarial activity, we studied the effects of extract and fractions of Phyllanthus nivosus leaf on Plasmodium lactate dehydrogenase (pLDH) activity using an in vitro assay. This was followed by an anti-plasmodial study using Plasmodium berghei-infected mice and an in silico identification of the plant's phytochemicals with possible pLDH-inhibitory activity. The activity of pLDH was significantly reduced in the presence of ethanol extract and various solvent fractions of Phyllanthus nivosus leaf, with the ethyl acetate fraction having the best inhibitory activity, which was comparable to that of the standard drug (chloroquine). The ethyl acetate fraction at 100 and 200 mg/Kg also suppressed the parasitaemia of Plasmodium berghei-infected mice by 76 and 80% respectively. Among the 53 compounds docked against pLDH, (-)-alpha-Cadinol, (+)-alpha-phellandrene, and spathulenol, all terpenes from the ethyl acetate fraction of P. nivosus leaf extract, demonstrated docking scores comparable to that of chloroquine. The three chemicals, like chloroquine, displayed important molecular interactions with the amino acid residues of the enzyme's NADH-binding site. According to the in silico ADMET study, the three terpenes have suitable drug-like abilities, pharmacokinetic features, and safety profiles. Hence, they could be considered for further development as antimalarial drugs.Communicated by Ramaswamy H. Sarma.

Metabolic recycling of storage lipids promotes squalene biosynthesis in yeast.

BACKGROUND: Metabolic rewiring in microbes is an economical and sustainable strategy for synthesizing valuable natural terpenes. Terpenes are the largest class of nature-derived specialized metabolites, and many have valuable pharmaceutical or biological activity. Squalene, a medicinal terpene, is used as a vaccine adjuvant to improve the efficacy of vaccines, including pandemic coronavirus disease 2019 (COVID-19) vaccines, and plays diverse biological roles as an antioxidant and anticancer agent. However, metabolic rewiring interferes with inherent metabolic pathways, often in a way that impairs the cellular growth and fitness of the microbial host. In particular, as the key starting molecule for producing various compounds including squalene, acetyl-CoA is involved in numerous biological processes with tight regulation to maintain metabolic homeostasis, which limits redirection of metabolic fluxes toward desired products. RESULTS: In this study, focusing on the recycling of surplus metabolic energy stored in lipid droplets, we show that the metabolic recycling of the surplus energy to acetyl-CoA can increase squalene production in yeast, concomitant with minimizing the metabolic interferences in inherent pathways. Moreover, by integrating multiple copies of the rate-limiting enzyme and implementing N-degron-dependent protein degradation to downregulate the competing pathway, we systematically rewired the metabolic flux toward squalene, enabling remarkable squalene production (1024.88 mg/L in a shake flask). Ultimately, further optimization of the fed-batch fermentation process enabled remarkable squalene production of 6.53 g/L. CONCLUSIONS: Our demonstration of squalene production via engineered yeast suggests that plant- or animal-based supplies of medicinal squalene can potentially be complemented or replaced by industrial fermentation. This approach will also provide a universal strategy for the more stable and sustainable production of high-value terpenes.

Borneol Ester Derivatives as Entry Inhibitors of a Wide Spectrum of SARS-CoV-2 Viruses.

In the present work we studied the antiviral activity of the home library of monoterpenoid derivatives using the pseudoviral systems of our development, which have glycoproteins of the SARS-CoV-2 virus strains Wuhan and Delta on their surface. We found that borneol derivatives with a tertiary nitrogen atom can exhibit activity at the early stages of viral replication. In order to search for potential binding sites of ligands with glycoprotein, we carried out additional biological tests to study the inhibition of the re-receptor-binding domain of protein S. For the compounds that showed activity on the pseudoviral system, a study using three strains of the infectious SARS-CoV-2 virus was carried out. As a result, two leader compounds were found that showed activity on the Wuhan, Delta, and Omicron strains. Based on the biological results, we searched for the potential binding site of the leader compounds using molecular dynamics and molecular docking methods. We suggested that the compounds can bind in conserved regions of the central helices and/or heptad repeats of glycoprotein S of SARS-CoV-2 viruses.

Therapeutic potential of plant secondary metabolites in treatment of respiratory viral diseases: A review

Respiratory viral infections are a major public health concern because of their global occurrence, ease of spread and considerable morbidity and mortality. Medical treatments for viral respiratory diseases primarily involve providing relief from symptoms like pain and discomfort rather than treating the infection. Very few antiviral medications have been approved with restrictive usage, high cost, unwanted side effects and limited availability. Plants with their unique metabolite composition and high remedial values offer unique preventive and therapeutic efficacy in treatment of viral infections. The present review is focused on the types and mode of action of plant secondary metabolites that have been used successfully ί in the treatment of infections caused by respiratory viruses like Influenza, SARS, MERS, RSV etc. Plant metabolites such as phenolics, alkaloids, terpenoids and oligosaccharides inhibit attachment and entry of the virus. Others such as flavonoids, viz quercetin and baicalein, alkaloids viz sanguinarine, berberine and emetine, specific lipids and fatty acids prevent viral replication and protein synthesis. These metabolites have the potential to be used as lead molecules that can be optimized to develop potent drugs for effectively combating pandemics caused by respiratory viruses.

Anti-Inflammatory and Antiviral Effects of Cannabinoids in Inhibiting and Preventing SARS-CoV-2 Infection.

The COVID-19 pandemic caused by the SARS-CoV-2 virus made it necessary to search for new options for both causal treatment and mitigation of its symptoms. Scientists and researchers around the world are constantly looking for the best therapeutic options. These difficult circumstances have also spurred the re-examination of the potential of natural substances contained in Cannabis sativa L. Cannabinoids, apart from CB1 and CB2 receptors, may act multifacetedly through a number of other receptors, such as the GPR55, TRPV1, PPARs, 5-HT1A, adenosine and glycine receptors. The complex anti-inflammatory and antiviral effects of cannabinoids have been confirmed by interactions with various signaling pathways. Considering the fact that the SARS-CoV-2 virus causes excessive immune response and triggers an inflammatory cascade, and that cannabinoids have the ability to regulate these processes, it can be assumed that they have potential to be used in the treatment of COVID-19. During the pandemic, there were many publications on the subject of COVID-19, which indicate the potential impact of cannabinoids not only on the course of the disease, but also their role in prevention. It is worth noting that the anti-inflammatory and antiviral potential are shown not only by well-known cannabinoids, such as cannabidiol (CBD), but also secondary cannabinoids, such as cannabigerolic acid (CBGA) and terpenes, emphasizing the role of all of the plant's compounds and the entourage effect. This article presents a narrative review of the current knowledge in this area available in the PubMed, Scopus and Web of Science medical databases.

Medicinal cannabis in Europe-An overview

Plants have been used for medicinal purposes long before prehistoric period. Among these ancient medicinal herbs, Cannabis, a flowering plant of the family Cannabaceae, originating from Central and South Asia, was used due to its broad-spectrum applications over the centuries. Its uses ranged from ropes, clothing, paper to its psychoactive properties, making it a very appealing plant. From the 1900's onwards cannabis consumption was deemed illegal in several countries around the world due to its overuse consequences [1]. The lack of scientific information regarding the mechanism of action of its constituents was a direct consequence from the illegal status given in the 1900's. Recently, this has changed, cannabis pre-clinical studies have shown several medicinal properties which helped cannabis gained traction and legal status for its medicinal use in most of North and South America, and in some European countries, lifting some of the old prejudice. In Europe, medicinal cannabis usage is still growing. Several cannabinoid-containing medicinal products are already available in the market [2,3]. EXMceuticals Portugal is one of the European Pharmaceutical companies working with medicinal cannabis that is specialized in extraction and purification of cannabinoids and terpenes for pharmaceutical grade ingredients. Most recently, due to the COVID-pandemic our research efforts have been put to "BioBlock COVID", a project that focus on antiviral properties of terpenes from cannabis and other medicinal plants for inactivation o the virus SARS-CoV-2, and its applications in tissues, hand and surface disinfectants.

Investigating the Anti-Viral and Anti-Bacterial activities of Jordanian Medicinal plants: A narrative review

The diversity in Jordan’s flora due to its geographical areas make is well noted in the scientific literature. The challenge of disease and death caused by infectious diseases like viruses and bacteria, and as infectious diseases evolve and pathogens develop resistance to existing pharmaceuticals, the search for new novel leads, possibly with different modes of action, against bacterial and viral diseases has intensified in recent years. The intent of this review is to provide prevalent information on the antibacterial and antiviral potential in medicinal plants in Jordan, mode of action, type of viruses and bacteria, and phytochemical contents. It has been demonstrated by several studies presented in this review that medicinal plants in Jordan are rich in phytochemicals and possess antiviral and antibacterial properties.

Virucidal Activity of Essential Oils From Citrus x aurantium L. Against Influenza A Virus H1N1: Limonene as a Potential Household Disinfectant Against Virus

This work explored the compositions of a crude extract of peels of Citrus x aurantium using a gas chromatography-mass spectrometry (GC-MS) technique. The crude extract of peels of C. × aurantium was analyzed by GC-MS revealing the presence of limonene as the major compound, accounting for 93.7% of the total. Virucidal activity of the oil of C. x aurantium peels against influenza A virus H1N1 was evaluated by the ASTM E1053-20 method. Moreover, the virucidal activity was also investigated of D-limonene, the major terpene in essential oils of C. x aurantium, and its enantiomer L-limonene. The essential oil of the C. x aurantium peels produced a log reduction of 1.9 to 2.0, accounting for 99% reduction of the virus, while D- and L-limonene exhibited virucidal activity with a log reduction of 3.70 to 4.32 at concentrations of 125 and 250.0 µg/mL, thus reducing the virus by 99.99%. Previous work found that D-limonene exhibited antiviral activity against herpes simplex virus, but L-limonene, an enantiomer of D-limonene, has never been reported for antiviral activity. This work demonstrates the antiviral activity of L-limonene for the first time. Moreover, this work suggests that concentrations of 0.0125% to 0.025% of either D- or L-limonene can possibly be used as a disinfectant against viruses, probably in the form of essential oil sprays, which may be useful disinfectants against the airborne transmission of viruses, such as influenza and COVID-19.

Cloning and functional characterization of a terpene synthase gene AlTPS1 from Atractylodes lancea

Atractylodes lancea (Thunb.) DC has been used widely as a medicinal herb for centuries and is now being used to treat COVID-19 pneumonia. Terpenoids are thought to be its main pharmacologically active constituents. However, their biosynthesis remains uncharacterized in this species. In this study, the terpene synthase gene AlTPS1 was cloned and functionally characterized. We found that AlTPS1 was a bifunctional enzyme that catalyzed the conversion of farnesyl diphosphate to nerolidol and geranyl diphosphate to linalool in vitro. However, it functioned only in the nerolidol production in vivo by transient expression of the AlTPS1 gene in Nicotiana benthamiana leaves maybe due to subcellular compartmentalization of the AlTPS1 in the cytosol. Furthermore, AlTPS1 was highly expressed in leaves, considered to be the sites of nerolidol synthesis. This study is the first in which the cloning and expression of the AlTPS1 gene from A. lancea were analyzed, and it has provided new insights into terpene biosynthesis in A. lancea.

Brazilian essential oils as source for the discovery of new anti-COVID-19 drug: a review guided by in silico study.

The emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in China and its spread worldwide has become one of the biggest health problem due to the lack of knowledge about an effective chemotherapy. Based on the current reality of the SARS-CoV-2 pandemic, this study aimed to make a review literature about potential anti-coronavirus natural compounds guided by an in silico study. In the first step, essential oils from native species found in the Brazilian herbal medicine market and Brazilian species that have already shown antiviral potential were used as source for the literature search and compounds selection. Among these compounds, 184 showed high antiviral potential against rhinovirus or picornavirus by quantitative structure-activity relationship analysis. (E)-α-atlantone; 14-hydroxy-α-muurolene; allo-aromadendrene epoxide; amorpha-4,9-dien-2-ol; aristochene; azulenol; germacrene A; guaia-6,9-diene; hedycaryol; humulene epoxide II; α-amorphene; α-cadinene; α-calacorene and α-muurolene showed by a molecular docking study the best result for four target proteins that are essential for SARS-CoV-2 lifecycle. In addition, other parameters obtained for the selected compounds indicated low toxicity and showed good probability to achieve cell permeability and be used as a drug. These results guided the second literature search which included other species in addition to native Brazilian plants. The majority presence of any of these compounds was reported for essential oils from 45 species. In view of the few studies relating essential oils and antiviral activity, this review is important for future assays against the new coronavirus. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s11101-021-09754-4.