Natural Therapeutics against the SARS-CoV-2 Viral infection

Urvashi Rai¹, Kavita Sharma¹, Richa Kamani¹, Urmila Pande¹, Alka Singh¹, Arjun Singh²*

¹Department of Pharmacognosy, School of Pharmaceutical Sciences,

Bhagwant University, Sikar Road, Ajmer, Rajasthan 305004, India.

²Department of Medicine, Sidney Kimmel Medical College,

Thomas Jefferson University, Philadelphia, PA 19107, United States.

*Corresponding Author E-mail: arjunphar@gmail.com

ABSTRACT:

Coronaviruses are a class of large, enveloped, positive-sensed, single-stranded RNA viruses that cause infections in the respiratory tracts of mammals such as humans, bats, and other animals. Coronavirus disease 2019 (COVID-19), also known as 2019 new coronavirus (2019-nCoV), is an agile respiratory disease caused by a novel coronavirus that was first discovered in Wuhan, China. It has now expanded to 216 nations and killed over 0.5 million people worldwide, prompting the World Health Organization (WHO) to proclaim it a pandemic. Current review focuses on the role of herbs and herbs-derived secondary metabolites in inhibiting the SARS-CoV-2 virus as well as in the management of post-COVID-19 complications. This strategy will promote and protect the use of medicinal plant resources to support the healthcare system. Plant-derived phytochemicals have already been shown to prevent viral infection and to alleviate post-COVID complications such as parkinsonism, kidney and heart failure, liver and lung damage, and mental problems. We investigated mechanistic approaches of herbal medicines and their phytochemicals as antiviral and post-COVID complications by modulating immunological and inflammatory states in this review.

KEYWORDS: SARS-CoV-2, Coronavirus, Natural products, Outbreak, Herbal medicine.

INTRODUCTION:

SARS-CoV-2, one of the most destructive viral epidemics since SARS-CoV and MERS, emerged in China's Wuhan city seafood market in December 2019¹. Close contact with infected people or exposure to coughing, sneezing, and respiratory droplets were identified to spread the virus^2-8. It has already been claimed that it has spread to 216 nations and killed over 0.5 million people. Brazil is now the new SARS-CoV-2 hotspot, following the United States, Russia, France, Italy, Germany, Spain, and the United Kingdom, where more than 11 million individuals have been infected⁹.

MATERIALS:

A phytopharmaceutical preparation derived solely from a whole plant or portions of a plant (flower, leaves, bark, stem, rhizome, root) or its exudates is referred to as an herbal intervention (resins, latex, gums)¹⁰. It is utilized either in its natural state or as a pure pharmaceutical formulation, such as extracts, juice, dry powder, decoction, and so on, after distillation, extraction, filtration, and so on¹¹. These are high in active metabolites, alkaloids, and flavonoids, which are responsible for their pharmacological activity. The importance of therapeutic herbs from various traditional medicine systems, as well as herbs-derived secondary metabolites, is discussed in this Review from a mechanistic standpoint for post-COVID related problems^12-19.

Major Plant chemical used for SARS-CoV-2 viral infection:

Due to the lengthy procedure of isolating the desired chemical, a large number of plant metabolites have remained undiscovered²⁰. Maceration, percolation, decoction, reflux extraction, soxhlet extraction, pressurized liquid extraction, supercritical fluid extraction, ultrasound assisted extraction, microwave-assisted extraction, pulsed electric field extraction, enzyme assisted extraction, hydro distillation, and steam distillation are now among the modern techniques used to isolate lead compounds from crude extracts. These methods may lead to the discovery of novel anti-SARS-CoV-2 compounds sooner than existing methods. Furthermore, plant metabolomics is being used to discover new pharmaceuticals from plant resources^21-22.

The active phytochemical elements of herbal formulations or medications, such as alkaloids, flavonoids, terpenoids, phenols, polyphenols, tannins, saponins, polysaccharides, proteins, lipids, and peptides, are responsible for their pharmacological action. The herbal medications utilized contain antipyretic, anti-inflammatory, expectorant, anti-asthmatic, antitussive, and antiviral activities that serve a variety of roles against virus invasion, penetration, reproduction, and expression. Potential SARS-CoV-2 protease inhibitors include Allium cepa, Aloe vera, Azadirachta indica, Cannabis sativa, Curcuma longa, Glycyrrhiza glabra, Nyctanthes arbortristis, Ocimum sanctum, Withania sominifera, and Zingiber officinale^23-27.

Many natural compounds have broad-spectrum antiviral action and have been utilized to treat SARS, MERS, influenza, and dengue virus. Major chemicals structures depict the chemical structures of bioactive phytomolecules that may be effective in the treatment of COVID-19-related problems. Furthermore, they have been reported to be immunomodulators, reducing the inflammatory impact that is responsible for the considerable morbidity and mortality associated with COVID-19 infection. The putative inhibitory mechanism of medicinal plants/products against SARS-CoV-2 viral replication is depicted in Figure. However, the phytochemicals may be harmful at high concentrations. However, the phytochemicals may be hazardous at certain quantities, thus in vitro and in vivo investigations are required to determine the safe and therapeutic levels for each natural ingredient before human clinical trials can begin. In their study, the focus on the potential usefulness of vitamins, probiotics, and nutraceuticals in reducing the likelihood of SARS-CoV-2 infection or moderating the symptoms of COVID-19^28-29.

Plant Source	Plant Parts	Family	Susceptible Virus	Status of the Antiviral Assay
Andrographis paniculata	Arial parts	Acanthaceae	Dengue virus serotype-1 (DENV-1)	In vitro
Avicennia marina	Leaf		Human immunodeficiency virus (HIV) and Herpis simplex virus (HSV)	In vitro
Baphicacanthuscusia	Root		Influenza A virus	In vitro and In vivo
Sambucus nigra	Flower and Leaf	Adoxaceae	Dengue virus serotype-2 (DENV-2)	In vitro
Sambucus nigra	Fruit		Infectious bronchitis virus (IBV) - chicken coronavirus	In vitro
IresineHerbstii	Leaf and Stem	Amaryllidaceae	Newcastle disease virus (NDV)	In vivo
Leucojum vernum	Bulb		HIV-1	In vitro
Anacardium occidentale	Leaf	Anacardiaceae	Simian (SA-11) virus	In vitro
Rhus aromatica	Bark		HSV-1 and HSV-2	In vitro
Rhus parviflora	Leaf		HIV-1	In vitro
Schinusterebinthifolia	Bark of Stem		HSV-1	In vitro and In vivo
Spondias lutea	Bark	Anacardiaceae	Human (HCR3) rotaviruses	In vitro
Spondias lutea L.	Leaf		Simian (SA-11) and human (HCR3) rotaviruses	In vitro
Angelica keiskei	Leaf	Apiaceae	Severe acute respiratory syndrome coronavirus (SARS-CoV)	In vitro and In silico
Carissa edulis	Root	Apocynaceae	HSV	In vitro and In vivo
Hemidesmus indicus	Root		HSV-1 and 2 HSV-2	In vitro
Arisaema tortuosum	Leaf	Araceae	Acyclovir-resistant HSV-2 and HSV-1	In silico
Panax ginseng	Root	Araliaceae	RSV	In-vitro and In vivo
Panax ginseng	Root		Murine norovirus (MNV) and Feline calicivirus (FCV)	In-vitro and In vivo
Panax ginseng	NR		Human rotavirus	In vitro
Panax notoginseng	Root		Influenza A H1N1 virus	In vitro and In vivo
Aloe arborescens	Leaf	Asphodelaceae	Influenza A and influenza B viruses	In vitro
Aloe vera	Leaf		HSV-2	In vitro
Achillea fragrantissima	Aerial part	Asteraceae	Poliomyelitis-1 virus	In vitro
Baccharis gaudichaudiana DC	NR		Bovine viral diarrhea virus, HSV-1, Poliovirus type 2 (PV-2) and vesicular stomatitis virus (VSV)	NR
Baccharis spicata (Lam.) Baill	NR		Bovine viral diarrhea virus (BVD), HSV-1, poliovirus type 2 (PV-2) and vesicular stomatitis virus (VSV)	NR
Bidens subalternans DC	NR		Bovine viral diarrhea virus, HSV-1, poliovirus type 2 (PV-2) and vesicular stomatitis virus	NR
Eupatorium perfoliatum	Aerial parts		Influenza A virus (IAV) H1N1	In vitro
Jasoniamontana	Aerial part		Poliomyelitis-1 virus	In vitro
Plucheasagittalis (Lam.) Cabrera	NR		Bovine viral diarrhea virus (BVDV) (HSV-1), poliovirus type 2 (PV-2) and vesicular stomatitis virus (VSV)	NR
Silybum marianum	NR		Chikungunya virus (CHIKV), Hepatitis C virus (HCV)	clinical presentations
Tagetes minuta L	NR	Asteraceae	Bovine viral diarrhea virus, HSV-1, poliovirus type 2 (PV-2) and vesicular stomatitis virus	NR
Tanacetum parthenium	Aerial part		HSV-1	In vitro and In vivo
Taraxacum officinale	Leaf		HCV	In-vitro and In silico
Taraxacum officinale	Herb		Influenza virus type A, H1N1.	In vitro
Tridaxprocumbers	Stem		Dengue virus serotype-2 (DENV-2)	In vitro
Vernonia cinerea	Leaf		Dengue virus serotype-2 (DENV-2)	In vitro
Balanites aegyptiaca	Leaf	Balanitaceae	VSV	In vitro
Epimedium koreanumNakai	Herb	Berberidaceae	Porcine epidermic diarrhea virus (PEDV)	In vitro and In vivo
Alnus japonica	Bark	Betulaceae	SARS-CoV	In vitro
Alnus japonica	Bark		Influenza virus KBNP-0028 (H9N2)	In vitro
Isatisindigotica	Root	Brassicaceae	SARS coronavirus	In vitro
Canarium album (Lour.)	Fruit (Fresh)	Burseraceae	Influenza A virus (IAV)	In vitro and In silico
Calophyllumbrasiliense	Leaf	Calophyllaceae	HIV-1	In vitro and In vivo
Capparis sinaica	Whole plant	Capparaceae	Avian influenza strain H5N1	In vitro
Capparis sinaica	Whole plant		HSV	In vitro
Capparis spinosa	Seed		HIV-1, HSV-2	In vitro
Cassinexylocarpa	Stem	Celastraceae	HIV	In vitro
Maytenuscuzcoina	Root bark		HIV	In vitro
Salacia reticulata	Stem and Root		Influenza A virus H1N1	In vitro and In vivo
Cistus incanus	Whole plant (Fresh)	Cistaceae	HIV (clinical HIV-1 and HIV-2 ) and Filoviruses, Ebola and Marburg virus	Clinically used
Tuberarialignosa	Whole plant		HIV	In vitro
Combretum adenogonium	Root and Stem bark	Combretaceae	HIV-1	In vitro
Terminalia mollis	Root and Bark		HSV-0	In vitro
Cornus canadensis	Leaf	Cornaceae	HSV-1	In vitro
Taxodium distichum	Stem	Cupressaceae	Influenza A and B viruses	In vitro
Cyperus rotundus	Rhizome	Cyperaceae	HSV-1, HBV	In vitro
Ephedra alata	Aerial part	Ephedraceae	HSV	In vitro
Equisetum giganteum	Root and Stem	Equisetaceae	HSV-2	In vitro and In vivo
Euphorbia denticulata	Aerial part	Euphorbiaceae	HSV	In vitro
Euphorbia hirta	Whole plant		HIV-1, HIV-2, SIV mac 251	In vitro
Euphorbia sikkimensis	Aerial parts		HIV-1	In vitro
Jatropha multifida	Stem		Influenza A H1N1 virus	In vitro
Acacia arabica	Leaf	Fabaceae	Influenza A virus H9N2	In vitro
Arachis hypogaea	Peanut skins		Human Influenza Viruses (type A and  B)	In vitro
Aspalathus linearis	Leaf		Rhesus rotavirus (RRV), Simian rotavirus (SA-11) infection	In vitro
Erythrina speciosa	Leaf		HSV-1	In vitro and In silico
Glycyrrhiza glabra L	Root		Rhesus rotavirus (RRV)	In vitro
Senna angustifolia	Leaf	Fabaceae	Dengue virus serotype-2 (DENV-2)	In vitro
Vachellianilotica	Bark		HSV-2	In vitro
Acacia catechu	Barks of stem		HIV-1	In vitro
Quercus brantii L Acorn.	Fruit	Fagaceae	HSV-1	In vitro
Quercus persica	Fruit		HSV-I	In vitro
Quercus persica	Fruit		HSV-2	In vitro
Geranium thunbergii	Aerial part (Dried)	Geraniaceae	Influenza virus, (H1N1, H3N2, Influenza type B	NR
Pelargonium sidoides	Root		HIV-1	In vitro
Pelargonium sidoides	Root		Influenza A virus strains (H1N1, H3N2), RSV, Human coronavirus, Parainfluenza virus, and Coxsackie virus	In vitro
Ribes nigrum	Fruit	Grossulariaceae	Influenza A virus	In vitro and In vivo
Hamamelis virginiana	Leaf and Bark	Hamamelidaceae	Influenza A Virus and Human Papillomavirus	In vitro
Hamamelis virginiana	Bark		HSV-1	NR
Melissa officinalis	Leaf and Stem (Dried)	Lamiaceae	Enterovirus 71	In vivo
Melissa officinalis	Oil		Enveloped herpesviruses	In vitro
Ocimum sanctum	Arial parts		Dengue virus serotype-1 (DENV-1)	In vitro
Ocimum sanctum	Leaf		Influenza A virus H9N2	In vitro
Prunella vulgaris	Spikes (dried)		HSV-1 and HSV-2 antigens virus antigen in Vero cells	In vitro
Prunella vulgaris	Plant and Seed		Lentivirus	In vitro
Prunellae Spica	Whole plant		Herpes simplex virus (HSV)	In vitro
Rosmarinus officinallis	Whole plant		HSV-1	In vitro
Schizonepeta tenuifolia Briq.	Lyophilized powder of herb		Enterovirus 71 (EV71)	In vitro and In vivo
Scutellariabaicalensis	Root		RSV, HIV, influenza, and Dengue viruses	In vivo
Laminaria japonica	Whole plant	Laminariaceae	RSV	In vitro
Lilium candidum	Stem, Leaf and Fruit	Liliaceae	HSV-1 and HSV-2 and Varicella-Zoster Virus (VZV)	In vitro
Lindernia crustacea	Whole plant	Linderniaceae	Epstein–Barr virus (EBV)	In vitro
Strychnospseudoquina	Bark of stem	Loganiaceae	HSV-1 (KOS strain) and HSV-2 (333 strain)	In vitro
Lagerstroemia speciosa	Leaf and Stem	Lythraceae	HIV-1	In vitro
Punica granatum	Fruit peel		HSV-2	In vitro
Punica granatum	Fruit juice		Influenza A virus	In vitro
Magnolia officinalis	Bark or Seed cones (fruit of conifers)	Magnoliaceae	Dengue virus Type 2	In vitro and Clinical application
Althaea officinalis	Leaf	Malvaceae	Influenza A virus H5N1	In vitro
Cissampelos pareira Linn	Aerial parts	Menispermaceae	Dengue virus types 1-4 (DENV-1-4)	In vitro and In vivo
Artocarpus integrifolia	Leaf, Flower, Seed and Bark	Moraceae	(SA-11) and human (HCR3) rotaviruses	In vitro
Ficus benjamina	Leaf		HSV-1 and HSV-2), Varicella Zoster Virus (VZV	In vitro
Ficus carica	Fruit latex		HSV-1, HSV-1, ECV-11 and ADV, influenza virus	In vitro
Ficus religiosa	Bark of stem		HSV-2	In vitro
Ficus septica	Leaves, Stem, Fruit, Heartwood		Dengue virus types 1-4 (DENV-1-4)	In vitro
Ficus sycomorus	Stem, Bark and Leaf	Moraceae	HSV-1	In vitro
Moringa peregrina	Seed	Moringaceae	HSV	In vitro
Myristica fragrans	Seed	Myristicaceae	Human (HCR3) rotaviruses	In vitro
Psidium guajava	Leaf	Myrtaceae	Simian (SA-11) virus	In vitro
Syzygiumaromaticum L.	Flower bud		HSV and HCV	In vitro
Peganum harmala	Seed	Nitrariaceae	HSV-2	In vitro
Paeonia delavayi	Root	Paeoniaceae	Influenza virus	In vitro
Paeonia lactiflora	Root		Influenza virus A/WSN/33 (H1N1)	In vitro and In vivo
Paulownia tomentosa	Fruit	Paulowniaceae	SARS-CoV papain-like protease (PLpro)	In vitro
Phyllanthus acidus	Bark and Root	Phyllanthaceae	Hepatitis B Virus	In vitro
Phyllanthus amarus	Root and Leaf		HCV	In vitro
Phyllanthus amarus	Harvested Plant		Acyclovir-resistant HSV strains, hepatitis B virus (HBV), HCV and HIV	In vitro
Phyllanthus niruri	Harvested plant	Phyllanthaceae	Acyclovir-resistant HSV strains, hepatitis B virus (HBV), HCV, HIV	In vitro
Phyllanthus urinaria	Harvested plants		Acyclovir-resistant HSV strains, hepatitis B virus (HBV), HCV and  HIV	In vitro
Phyllanthus watsonii	Harvested plant		Acyclovir-resistant HSV strains, hepatitis B virus (HBV), HCV and HIV	In vitro
Pinus yunnanensis	Cone (contains the reproductive organs	Pinaceae	HIV-1	In vitro
Limonium sinense	Underground part/Root	Plumbaginaceae	HCV	In vitro
Plumbago indica	Root		Influenza A (H1N1)	In vitro and In silico
Rheum tanguticum	Root	Polygonaceae	HSV-1 and HSV -2	In vitro and In vivo
Ardisia chinensis Benth	Whole plant	Primulaceae	Coxsackie B3 Virus	In vitro
Embeliaribes	Fruit	Primulaceae	Influenza virus A/Puerto Rico/8/34 (H1N1)	In vitro and In silico
Coptis chinensis	Root	Ranunculaceae	HCV	In vitro and In vivo
Coptisdeltoidea	Root		HCV	In vitro and In vivo
Agrimonia pilosa	Whole plant (Dried)	Rosaceae	Influenza viruses (H1N1 and H3N2)	In vitro and  In vivo
Prunus dulcis	Peel of seed		HSV-1	In vitro
Morindacitrifolia	Leaf	Rubiaceae	HCV	In vitro
Pavetta tomentosa	Leaf		Dengue virus (DENV)	In vitro and in vivo
Tarenna asiatica	Leaf		Dengue virus (DENV)	In vitro and In vivo
Aegle marmelos	Fruit (unripen)	Rutaceae	Human coxsackieviruses B1-B6, Rotavirus SA-11	In vitro
Dimocarpus longan	Leaf	Sapindaceae	HCV (genotype 2a strain JFH1)	In vitro
Saururus chinensis Baill	Aerial part	Saururaceae	Coxsackievirus B3 (CVB3)	In vitro
Illicium verum Hook. f.	Fruit	Schisandraceae	Grouper iridovirus infection (GIV)	In vitro and In vivo
Tamarixnilotica	Aerial part	Tamaricaceae	HSV	In vitro
Torreya nucifera	Leaf	Taxaceae	SARS-CoV 3CLpro	In vitro and In silico
Camellia sinensis	Natural green tea extract	Theaceae	HIV, HTLV-1, HCV, Influenza and HBV	In vitro and clinical applicat-ion
Viola diffusa	Whole plant	Violaceae	Hepatitis B Virus	In vitro
Alpinia katsumadai	Seed	Zingiberaceae	influenza virus type A	In vitro
Allium sativum L.		Amaryllidaceae	SARS-CoV‑2	Molecular docking
Torilis fructus	Plant Material	Apiaceae	SARS-CoV	in vitro
Lycoris radiata	Stem	Amaryllis	SARS-CoV	in vitro
Acanthopanacis cortex	Plant Material	Araliaceae	SARS-CoV	in vitro
Anthemis hyaline	flowers and buds	Asreraceae	SARS-CoV	in vitro
Tripterygium regelii	stem root	Celastraceae	SARS-CoV	in vitro
Juniperus oxycedrus	Berry	Cupressaceae	HSV-1	in vitro
Caesalpinia sappan	-	Fabaceae	SARS-CoV-2	Molecular docking
Cassia tora	seed	Fabaceae	SARS-CoV	in vitro
Psoralea corylifolia	seed	Fabaceae	SARS-CoV	in vitro
Gentiana scabra	Rhizome	Gentianaceae	SARS-CoV	in vitro
Cinnamomum verum	inner bark	Lauraceae	SARS-CoV	in vitro
Laurus nobilis	Berry	Lauraceae	SARS-CoV	in vitro
Taxillus chinensis	Stem	Loranthaceae	SARS-CoV	in vitro
Polygonum multiflorum	Root tuber, Vines	Polygonaceae	SARS-CoV	in vitro
Rheum officinale	Root tuber	Polygonaceae	SARS-CoV	in vitro
Rheum palmatum	roots and rhizomes	Polygonaceae	SARS-CoV	in vitro
Nigella sativa	seeds	Ranunculaceae	SARS-CoV	in vitro
Citrus sinensis	peels	Rutaceae	SARS-CoV	in vitro
Alpinia galanga	-	Zingiberaceae	SARS-CoV-2	Molecular docking

CONCLUSION:

The findings of this systematic review indicate that using herbal remedies as an adjunct to Western Medicine treatment has an additional good effect and is likely to help relieve the core symptoms of COVID-19 disease (e.g., fever, cough, exhaustion) in a comparatively shorter length of time^31-35. The effect rate, chest CT pictures, WBC count, absolute lymphocyte count, lymphocyte percentage, and C-Reactive protein level all improved. However, because of the scarcity of high-quality clinical trials and the significant degree of variability in the included research, a more definitive conclusion on the effects of herbal therapies on lowering body temperature and adverse effects could not be reached at this time. There are some differences in the therapeutic effects of different herbal therapies^36-41.

CONFLICT OF INTEREST:

The author has no conflicts of interest.

ACKNOWLEDGMENTS:

The author would like to thank NCBI, PubMed and Web of Science for the free database services for their kind support during this study.

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8. Khwaja, Sadiya, Kaneez Fatima, Mohammad Hasanain, Chittaranjan Behera, AvneetKour, Arjun Singh, SuaibLuqman, et al. “Antiproliferative Efficacy of Curcumin Mimics through Microtubule Destabilization.” European Journal of Medicinal Chemistry 151 (May 2018): 51–61. https://doi.org/10.1016/j.ejmech.2018.03.063.

9. Kumar, Balagani Sathish, Kusumoori Ravi, Amit Kumar Verma, Kaneez Fatima, Mohammad Hasanain, Arjun Singh, Jayanta Sarkar, Suaib Luqman, Debabrata Chanda, and Arvind S. Negi. “Synthesis of Pharmacologically Important Naphthoquinones and Anticancer Activity of 2-Benzyllawsone through DNA Topoisomerase-II Inhibition.” Bioorganic & Medicinal Chemistry 25, no. 4 (February 2017): 1364–73. https://doi.org/10.1016/j.bmc.2016.12.043.

10. Mishra, Disha, Jyotshna, Arjun Singh, D. Chanda, K. Shanker, and Puja Khare. “Potential of Di-Aldehyde Cellulose for Sustained Release of Oxytetracycline: A Pharmacokinetic Study.” International Journal of Biological Macromolecules 136 (September 2019): 97–105. https://doi.org/10.1016/j.ijbiomac.2019.06.043.

11. Sathish Kumar, B., Amit Kumar, Jyotsna Singh, Mohammad Hasanain, Arjun Singh, Kaneez Fatima, Dharmendra K. Yadav, et al. “Synthesis of 2-Alkoxy and 2-Benzyloxy Analogues of Estradiol as Anti-Breast Cancer Agents through Microtubule Stabilization.” European Journal of Medicinal Chemistry 86 (October 2014): 740–51. https://doi.org/10.1016/j.ejmech.2014.09.033.

12. Sathish Kumar, B., Aastha Singh, Amit Kumar, Jyotsna Singh, Mohammad Hasanain, Arjun Singh, Nusrat Masood, et al. “Synthesis of Neolignans as Microtubule Stabilisers.” Bioorganic & Medicinal Chemistry 22, no. 4 (February 2014): 1342–54. https://doi.org/10.1016/j.bmc.2013.12.067.

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16. Singh, Arjun, B. Sathish Kumar, Hina Iqbal, Sarfaraz Alam, Pankaj Yadav, Amit Kumar Verma, Feroz Khan, et al. “Antihypertensive Activity of Diethyl-4,4’-Dihydroxy-8,3’-Neolign-7,7’-Dien-9,9’-Dionate: A Continuation Study in L-NAME Treated Wistar Rats.” European Journal of Pharmacology 858 (September 5, 2019): 172482. https://doi.org/10.1016/j.ejphar.2019.172482.

17. Singh, Arjun, Ipsita Mohanty, Jagmohan Singh, and Satish Rattan. “BDNF Augments Rat Internal Anal Sphincter Smooth Muscle Tone via RhoA/ROCK Signaling and Nonadrenergic Noncholinergic Relaxation via Increased NO Release.” American Journal of Physiology-Gastrointestinal and Liver Physiology 318, no. 1 (January 1, 2020): G23–33. https://doi.org/10.1152/ajpgi.00247.2019.

18. Singh, Arjun, and Satish Rattan. “BDNF Rescues Aging-Associated Internal Anal Sphincter Dysfunction.” American Journal of Physiology-Gastrointestinal and Liver Physiology 321, no. 1 (July 1, 2021): G87–97. https://doi.org/10.1152/ajpgi.00090.2021.

19. Singh, Arjun, Jagmohan Singh, and Satish Rattan. “Evidence for the Presence and Release of BDNF in the Neuronal and Non‐neuronal Structures of the Internal Anal Sphincter.” Neurogastroenterology& Motility, February 24, 2021. https://doi.org/10.1111/nmo.14099.

20. Srivastava, Ankita, Kaneez Fatima, Eram Fatima, Arjun Singh, Aastha Singh, Aparna Shukla, Suaib Luqman, et al. “Fluorinated Benzylidene Indanone Exhibits Antiproliferative Activity through Modulation of Microtubule Dynamics and Antiangiogenic Activity.” European Journal of Pharmaceutical Sciences 154 (November 1, 2020): 105513. https://doi.org/10.1016/j.ejps.2020.105513.

21. Arjun Singh. A Review of various aspects of the Ethnopharmacological, Phytochemical, Pharmacognostical, and Clinical significance of selected Medicinal plants. Asian Journal of Pharmacy and Technology; 12(4):349-0. doi: 10.52711/2231-5713.2022.00055

22. Manmohan, S., Arjun, S., Khan, S. P., Eram, S., &Sachan, N. K., 2012. Green chemistry potential for past, present and future perspectives. International Research Journal of Pharmacy, 3, 31-36.

23. Singh A, Kumar BS, Alam S, Iqbal H, Shafiq M, Khan F, Negi AS, Hanif K, Chanda D. Corrigendum to "Diethyl-4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate exhibits AH activity in rats through increase in intracellular cGMP level and blockade of calcium channels" [Eur. J. Pharmacol. 799 (2017) 84-93]. Eur J Pharmacol. 2017 Jul 5;806:111. doi: 10.1016/j.ejphar.2017.04.033. Erratum for: Eur J Pharmacol. 2017 Mar 15;799:84-93. PMID: 28495016.

24. Singh, A., R. Sharma, K. M. Anand, S. P. Khan, and N. K. Sachan. "Food-drug interaction." International Journal of Pharmaceutical & Chemical Science 1, no. 1 (2012): 264-279.

25. Singh, A., Chanda, D., & Negi, A. S. (2018). Antihypertensive activity of Diethyl-4, 4'-dihydroxy-8, 3'-neolign-7, 7'-dien-9, 9'-dionate through increase in intracellular cGMP level and blockade of calcium channels (VDCC) and opening of potassium channel and in vivo models (SHRs and L-NAME induced hypertension). In Proceedings for Annual Meeting of The Japanese Pharmacological Society WCP2018 (The 18th World Congress of Basic and Clinical Pharmacology) (pp. PO1-2). Japanese Pharmacological Society.

26. Yadav P, Iqbal H, Kumar K, Kumar P, Mishra P, Singh A, Pal A, Mukhopadhay P, Negi AS, Chanda D. "Novel naphthoquinone 2-benzyllawsone protects against sepsis through reversal of vascular hyporeactivity and hypotension, inhibition of inflammation and anti-microbial activity in Swiss albino mice." European Journal of Pharmacology; 2022 Feb 15; 917:174757. DOI: https://doi.org/10.1016/j.ejphar.2022.174757  

27. Singh A., Singh J, Rattan S. "Evidence for the presence and release of BDNF in the neuronal and non-neuronal structures of the internal anal sphincter."  Neurogastroenterol Motility. 2021 Feb 24;e14099. DOI: https://doi.org/10.1111/nmo.14099

28. Singh, Arjun, B. Sathish Kumar, Hina Iqbal, Sarfaraz Alam, Pankaj Yadav, Amit Kumar Verma, Feroz Khan, et al. "Antihypertensive Activity of Diethyl-4,4'-Dihydroxy-8,3'-Neolign-7,7'-Dien-9,9'-Dionate: A Continuation Study in L-NAME Treated Wistar Rats." European Journal of Pharmacology 858 (2019): 172482. DOI: https://doi.org/10.1016/j.ejphar.2019.172482

29. Hamid, A. A., Tanu Kaushal, Raghib Ashraf, Arjun Singh, Amit Chand Gupta, Om Prakash, Jayanta Sarkar, et al. "(22Œ≤,25R)-3Œ≤-Hydroxy-Spirost-5-En-7-Iminoxy-Heptanoic Acid Exhibits Anti-Prostate Cancer Activity through Caspase Pathway." Steroids 119 (2017): 43-52. DOI: https://doi.org/10.1016/j.steroids.2017.01.001  

30. Singh, Arjun, B. Sathish Kumar, Sarfaraz Alam, Hina Iqbal, et al. "Diethyl-4,4'-dihydroxy-8,3'-neolign-7,7'-dien-9,9'-dionate exhibits antihypertensive activity in rats through increase in intracellular cGMP level and blockade of calcium channels." European Journal of Pharmacology 799 (2017): 84-93. DOI: https://doi.org/10.1016/j.ejphar.2017.01.044

31. Shilpi Jain, Arjun Singh, Puja Khare, D. Chanda, Disha Mishra, Karuna Shanker, Tanmoy Karak. "Metal bioavailability and toxicity of Bacopa monnieri grown in Biochar amended mine waste contaminated soil." Ecological Engineering, 108 (2017): 211-219. DOI: https://doi.org/10.1016/S2095-4964(16)60241-8

32. Gautam, Yashveer, Sonam Dwivedi, Ankita Srivastava, Hamidullah, Arjun Singh, et al. "2-(3′,4′-Dimethoxybenzylidene) tetralone Induces anti-breast cancer activity through Microtubule Stabilization and Activation of Reactive Oxygen Species." RSC Advances 6, 40 (2016): 33369-79. DOI: https://doi.org/10.1039/C6RA02663J

33. Chanda, Debabrata, Jesus Prieto-Lloret, Arjun Singh, Hina Iqbal, Pankaj Yadav, Vladimir Snetkov, and Philip I. Aaronson. "Glabridin-induced vasorelaxation: Evidence for a role of BKCa channels and cyclic GMP." Life Sciences 165 (2016): 26-34. DOI: https://doi.org/10.1016/j.lfs.2016.09.018

34. Hamid, A. A., Mohammad Hasanain, Arjun Singh, BalakishanBhukya, et al. "Synthesis of novel anticancer agents through opening of spiroacetal ring of Diosgenin." Steroids 87 (2014): 108-18. DOI: https://doi.org/10.1016/j.steroids.2014.05.025

35. Singh, A. (2023). An Overview on Phytoestrogen based antihypertensive agent for their potential Pharmacological Mechanism. Research Journal of Pharmaceutical Dosage Forms and Technology, 15(3), 211-214.

36. Tim F. Dorweiler, Arjun Singh, Richard N Kolesnick, Julia V. Busik; Inhibition of ceramide rich platforms by anti-ceramide immunotherapy prevents retinal endothelial cell damage and the development of diabetic retinopathy.. Invest. Ophthalmol. Vis. Sci. 2023;64(8):941.

37. Singh, Arjun, Rupendra Kumar, and Sachin Sharma. "Natural products and Hypertension: Scope and role in Antihypertensive Therapy." Asian Journal of Nursing Education and Research 13.2 (2023): 162-166.DOI:10.52711/2349-2996.2023.00035

38. Devender Paswan, Urmila Pande, Alka Singh, Divya Sharma, Shivani Kumar, Arjun Singh. Epidemiology, Genomic Organization, and Life Cycle of SARS CoV-2. Asian Journal of Nursing Education and Research. 2023; 13(2):141-4. doi: 10.52711/2349-2996.2023.00031

39. Singh, Arjun; Kumar, Rupendra.  “An Overview on Ethnopharmacological, Phytochemical, and Clinical Significance of Selected Dietary Polyphenols”. Asian Journal of Research in Chemistry; Raipur Vol. 16, Iss. 1,  (Jan/Feb 2023): 8-12. DOI:10.52711/0974-4150.2023.00002

40. Singh, Arjun.  “Plant-based Isoquinoline Alkaloids: A Chemical and Pharmacological Profile of Some Important Leads”. Asian Journal of Research in Chemistry; Raipur Vol. 16, Iss. 1,  (Jan/Feb 2023): 43-48. DOI:10.52711/0974-4150.2023.00008.

41. Arjun Singh. Plant-based Isoquinoline Alkaloids: A Chemical and Pharmacological Profile of Some Important Leads. Asian Journal of Research in Chemistry. 2023; 16(1):43-8. doi: 10.52711/0974-4150.2023.00008

Received on 07.01.2023 Modified on 23.06.2023

Accepted on 16.09.2023 ©Asian Pharma Press All Right Reserved

Asian J. Res. Pharm. Sci. 2024; 14(1):27-33.

DOI: 10.52711/2231-5659.2024.00005