Department of Basic Medical Sciences, College of Medicine at Shaqra, Shaqra University, Saudi Arabia.
The global health pandemic of coronavirus disease (Covid-19) did not have specifically approved medication for the treatment. To maintain the human immunity power by natural remedies is the only way to prevent coronavirus infection. We designed a study protocol by selecting 10 natural plant active constituents that were claimed by traditional and investigational ways to have anti-inflammatory, antioxidant, immunomodulatory, and antiviral properties. We will analyze these selected 10 plants’ active constituents by molecular docking analysis. This article is a literature review of selected 10 plants products including Coffea Arabica, Curcuma longa, Glycyrrhiza glabra, Zizyphus vulgaris, Sisymbrium irio, Borago officinalis, Althaea officinalis, Malva sylvestris, Cordia Latifolia, and Adhatoda vasica for their anti-inflammatory, antioxidant, immunomodulatory, and antiviral properties.
Keywords COVID-19, molecular docking, antiviral, antiinflammatory, antioxidant, immunomodulator
An extensive literature review was made by using PubMed and PubChem database on selected 10 plants products including Coffea Arabica, Curcuma longa, Glycyrrhiza glabra, Zizyphus vulgaris, Sisymbrium irio, Borago officinalis, Althaea officinalis, Malva sylvestris, Cordia Latifolia, and Adhatoda vasica for their antiinflammatory, antioxidant, immunomodulatory and antiviral properties.
Coffee has been studied for its health benefits, including the prevention of several chronic diseases, such as type 2 diabetes mellitus, cancer, Parkinson’s, and liver diseases. Chlorogenic acid (CGA), an important component in coffee beans, was shown to possess antiviral activity against viruses. Coffea arabica extract (CAE) containing 48.3 ± 0.4 mg/g of chlorogenic acid and a trace amount of caffeic acid was found to alleviate photoaging activity in human skin fibroblasts. In this study, polyphenol-rich CAE was investigated for its antioxidant and anti-inflammatory properties. Many pharmacological activities are attributed to these components that include anti-oxidant, anti-inflammatory, immunomodulatory, antimicrobial, anti-cancer, cardioprotective, and neuroprotective effects. In one study, the antioxidant performance, nutritional composition, long-distance transport of Se, photosynthetic pigments, and growth of Coffea arabica genotypes in response to Se concentration in solution were evaluated. These results suggest that antioxidant metabolism was effective in regulating oxidative stress in plants treated with Se. The increase in sucrose, and decrease in SOD, CAT, and ascorbate peroxidase (APX) activities, as well as Se compartmentalization in the roots, were the main biochemical and physiological modulatory effects of coffee seedlings under stress conditions due to excess of Se. The expression of mRNA for tumor necrosis factor-alpha and interleukin-6 was decreased in cells treated with the coffee extracts and the expression decreased with increasing roasting levels. These data suggest that coffee has physiological antioxidant and anti-inflammatory activities and these effects are negatively correlated with roasting levels in the cell models.
One study revealed the potential antiviral activity of Curcuma longa against H9N2 influenza viruses and can be opted as an alternative to antibiotics and antiviral drugs to minimize the antimicrobial resistance in the human and animal population. Human studies have found some evidence of the anti-inflammatory activity of curcumin. The laboratory studies have identified many different molecules involved in inflammation that are inhibited by curcumin including phospholipase, lipooxygenase, cyclooxygenase 2, leukotrienes, thromboxane, prostaglandins, nitric oxide, collagenase, elastase, hyaluronidase, monocyte chemoattractant protein-1, interferon-inducible protein, tumor necrosis factor (TNF), and interleukin-12 (IL-12). Curcumin has been demonstrated to be safe in six human trials and has demonstrated antiinflammatory activity. It may exert its anti-inflammatory activity by inhibiting many different molecules that play a role in inflammation. Curcumin (diferuloylmethane) is an active ingredient in turmeric (Curcuma longa) with anti-inflammatory, antioxidant, chemopreventive, chemosensitization, and radiosensitization properties. Conjugation of curcumin (Curc) to albumin (Alb) has been found to increase the aqueous solubility of the drug. Results of the present study suggest that curcumin albumin conjugate has immunomodulatory and tumor growth inhibition properties.
In one study the effect of extracts from Glycyrrhiza glabra leaves was investigated against Newcastle disease virus (NDV) by an in-vivo assay. Seven groups of nine-day-old embryonated chicken eggs were inoculated with various treatments of different plant extracts. Results have verified that all the extracts especially that of methanol 300ìg/mL from leaves of Glycyrrhiza glabra have strong antiviral activity against NDV in vivo. Pharmacological experiments have demonstrated that different extracts and pure compounds from this species exhibit a broad range of biological properties, including antibacterial, antiinflammatory, antiviral, antioxidant, and antidiabetic activities. One study analyzed the molecular interactions of protein-phytocompounds, by AutoDock Vina 4.2 tools. The best interactions of each algorithm were subjected to molecular dynamic (MD) simulations to have an insight into the molecular dynamic mechanisms involved. Selected phytoconstituents gave a good score for binding affinity with the main protease 6LU7 of SARS CoV-2 as compared to the antiviral drugs already being used in the disease therapy.
In recent years, jujube fruit (Zizyphus vulgaris L.) has been reported to have anti-inflammatory effects as a traditional therapeutic agent. Therefore, the study was conducted to investigate the effects of jujube fruit extract on second-degree burn wounds among Balb/c mice. The results of the study indicated that the jujube fruit extract could accelerate burn wound healing among Balb/c mice. A pilot study revealed that a 40 μl dose of 107 CFU/ml could induce infection which persists up to 08 days post-infection. Mice treated with T. vulgaris and Z. jujuba showed a reduction in gross lesion score of both heart and lungs. Treatment with only some plants could significantly decrease the bacterial load of the throat (T. vulgaris) heart, blood, and joint (C. latifolia, and T. vulagris). This was the first report confirming in vivo anti-MRSA potential of C. latifolia and T. vulgaris and highlight the need to explore bioactive constituents of these plants.
Crude extracts of the seeds of Sisymbrium irio L. were tested for antipyretic, analgesic, and antimicrobial effects. The ethanolic extract exhibited significant antipyretic (Onset: < 1 hour, peak: 3 hours, duration: > 5 hours; p < 0.05) and analgesic (p < 0.001) effects. It also exhibited marked antibacterial action against both gram-positive and gram-negative organisms and was found to be nontoxic in acute studies. To combat the multidrug-resistant (MDR) superbugs, silver nanoparticles (Ag NPs) were synthesized using an aqueous leaf extract of seasonal desert plant Sisymbrium irio obtained from the central region of Saudi Arabia by a simple one-step procedure. The physical and chemical properties of the Ag NPs were investigated through ultraviolet-visible analysis (UV-vis), Fourier-transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), scanning electron microscope (SEM), and transmission electron microscope (TEM) analysis. In conclusion, the newly synthesized Ag NPs could be a potential alternative candidate in biomedical applications in controlling the spread of MDR pathogens.
Antioxidant activity of Borago officinalis was evaluated by using a 2, 2-diphenyl-1-picryl-hydrazylhydrate assay. The data of the study showed that the extracts of Borago officinalis possess antioxidant and free radical scavenging activities. Borage (Borago officinalis) is a plant with nutritional value that is also used in traditional medicine to treat gastrointestinal diseases. The study investigated the amoebicidal activity of a methanol extract of borage. The 50% inhibitory concentration (IC..) of the extract for Entamoeba histolytica was 33 ƒÊg/mL. The 50% lethal dose of the extract for brine shrimp was greater than 1,000 ƒÊg/mL. The IC.. of the extract for Vero cells was 203.9 ƒÊg/mL. These results support the use of borage to prevent diseases associated with E. histolytica infection. Common antiinflammatory herbal plants are Curcuma longa, Zingiber officinale, Rosmarinus officinalis, Borago officinalis, Urtica dioica, Uncaria tomentosa, Vaccinium myrtillus, Olea europaea and much more. They are believed to be without side effects unlike the chemical counterparts or synthetic anti-inflammatory agents e.g. steroids, nonsteroid anti-inflammatory drugs, and immunosuppressants used for controlling and suppressing inflammatory crisis.
One study was aimed at experimental confirmation of Althaea officinalis polysaccharide rhamnogalacturonan antitussive effect and its changes in conditions of allergic inflammation. Rhamnogalacturonan isolated from Althaea officinalis mucilage possesses a very high cough suppressive effect in guinea pigs test system, which is shortened in conditions of experimentally induced airways allergic inflammation. One study investigates the potential role of aqueous extract of Althaea officinalis flower in lipemia, gastric ulcer, inflammation, and platelet aggregation using the rat model. The aqueous extract of Althaea officinalis flower demonstrated potential benefits in lipemia, inflammation, gastric ulcer, and platelet aggregation with no visible adverse effect. The study aimed to inspect gastro-protective as well as in vitro and in vivo antioxidant potential of Althaea officinalis and Solanum nigrum extracts on pyloric-ligation/indomethacin-induced gastriculceration in rats. Reduction in titratable acidity, gastric mucosal nitric-oxide, antioxidant contents, and protective factors accompanied gastric-ulceration. Additionally, elevation in pro-inflammatory cytokines content and reduction in cystathionine-â-synthase and heme-oxygenase-1 expression was witnessed. Omeprazole, misoprostol, Althaea officinalis, and Solanum nigrum pretreatments fixed blood and tissue biomarkers, thereby protecting them from pyloric-ligation/indomethacin-induced gastric ulceration in rats, which is hopeful for clinical examinations.
The emphasis of the study is to evaluate a natural product and the potential microbicide activity using a dual-chamber infection method. Malva sylvestris extracts and fractions were screened for anti-HIV activity by measuring the virus-antibody neutralization. Natural occurring derivatives of M. sylvestris demonstrated to work inhibiting reverse transcriptase enzyme action. M. sylvestris contains highly potential anti-HIV-1 BaL components and may be considered a potential source for new formulations in the development of topical microbicides. The effects of extraction temperature, extraction time, the ratio of water to raw material, and the number of extraction on the extraction yield of crude polysaccharides from the leaves of Malva sylvestris (MSLCP) were optimized by statistical analysis using response surface methodology. The response surface methodology (RSM) was used to optimize MSLCP extraction yield by implementing the CCD design. The results demonstrated that MSLCP had strong scavenging activities in vitro on DPPH and hydroxyl radicals. Overall, MSLCP may have potential applications in the medical and food industries.
Recently, one study reported high in vitro antibacterial efficacy of Althaea officinalis, Ziziphus jujuba, Cordia latifolia, and Thymus vulgaris out of a total of  plants against a wide range of bacteria including MRSA. This study was, therefore, designed to confirm the efficacy of these four herbs against MRSA in an animal model. This is the first report confirming in vivo anti-MRSA potential of C. latifolia and T. vulgaris and highlights the need to explore bioactive constituents of these plants. Moreover, the previously reported in vitro antibacterial efficiency of A. officinalis could not be validated in the current study. The in vitro antibacterial activities of 29 traditional medicinal plants used in respiratory ailments were assessed on multidrug-resistant Gram-positive and Gram-negative bacteria isolated from the sore throat patients and two reference strains. Methanolic extract of 18 plants showed antimicrobial activity against test strains Cordia latifolia (ZI = 16-20 mm, MIC: 12.62-62.5 μg/mL) showed significant antibacterial activity. The results obtained from this study provide a scientific rationale for the traditional use of these herbs and laid the basis for future studies to explore novel antimicrobial compounds.
COVID-19 pneumonia has been associated with severe acute hypoxia, sepsis-like states, thrombosis, and chronic sequelae including persisting hypoxia and fibrosis. The molecular hypoxia response pathway has been associated with such pathologies and our recent observations on anti-hypoxic and antiinflammatory effects of whole aqueous extract of Adhatoda Vasica (AV) prompted us to explore its effects on relevant preclinical mouse models. Results provide a scientific rationale for this ayurvedic herbal medicine in ameliorating the hypoxia-hyperinflammation features and highlights the repurposing potential of AV in COVID-19-like conditions. Methanolic extract of Adhatoda vasica L. leaves (MEAV) was analyzed by hyphenated gas chromatography-mass spectroscopy for identification and characterization of its bioactive and traditional therapeutic claim. Methanolic extract of Adhatoda vasica L. leaves consists of both polar and nonpolar components. GC-MS analysis was used to identify these compounds. The current work validates that the antioxidant activity of the methanolic extract was attributed to the presence of compounds like vitamin E, alkaloid, and terpene. PubMed and PubChem database literature review on selected 10 plants products including Coffea Arabica, Curcuma longa, Glycyrrhiza glabra, Zizyphus vulgaris, Sisymbrium irio, Borago officinalis, Althaea officinalis, Malva sylvestris, Cordia Latifolia and Adhatoda vasica indicate that these plant products and their active constituents have significant anti-inflammatory, antioxidant, immunomodulatory and antiviral properties.
The authors declare that there are no conflicts of interest relevant to this article.
The authors extend their appreciation to the Deputyship of Research and Innovation, Ministry of Education in Saudi Arabia for funding this research work through the project number IFP2021-090.
- 1.Muchtaridi M, Lestari D, Khairul Ikram NK, Gazzali AM, Hariono M, Wahab HA. Decaffeination and Neuraminidase Inhibitory Activity of Arabica Green Coffee (Coffea arabica) Beans: Chlorogenic Acid as a Potential Bioactive Compound. Molecules. 2021 Jun 4;26(11):3402. [Google Scholar]
- 2.Wu PY, Huang CC, Chu Y, Huang YH, Lin P, Liu YH, Wen KC, Lin CY, Hsu MC, Chiang HM. Alleviation of Ultraviolet B-Induced Photodamage by Coffea arabica Extract in Human Skin Fibroblasts and Hairless Mouse Skin. Int J Mol Sci. 2017 Apr 7;18(4):782. [Google Scholar]
- 3.Islam MT, Tabrez S, Jabir NR, Ali M, Kamal MA, da Silva Araujo L, De Oliveira Santos JV, Da Mata AMOF, De Aguiar RPS, de Carvalho Melo Cavalcante AA. An Insight into the Therapeutic Potential of Major Coffee Components. Curr Drug Metab. 2018;19(6):544-556. [Google Scholar]
- 4.Mateus MPB, Tavanti RFR, Galindo FS, Silva ACDR, Gouveia GCC, Aparecido CFF, Carr NF, Feitosa YB, Santos EF, Lavres J, Reis ARD. Coffea arabica seedlings genotypes are tolerant to high induced selenium stress: Evidence from physiological plant responses and antioxidative performance. Ecotoxicol Environ Saf. 2020 Oct 15;203:111016. [Google Scholar]
- 5.Jung S, Kim MH, Park JH, Jeong Y, Ko KS. Cellular Antioxidant and Anti-Inflammatory Effects of Coffee Extracts with Different Roasting Levels. J Med Food. 2017 Jun;20(6):626-635. [Google Scholar]
- 6.Shah SIA, Tipu MY, Aslam A, Khan AU, Shafee M, Khan SA, Khan NU, Akbar A. Elucidating antiviral activity of Curcuma longa against H9 N2 influenza virus using embryonated chicken egg model. Trop Biomed. 2021 Sep 1;38(3):353-359. [Google Scholar]
- 7.Chainani-Wu N. Safety and anti-inflammatory activity of curcumin: a component of tumeric (Curcuma longa). J Altern Complement Med. 2003 Feb;9(1):161-8. [Google Scholar]
- 8.Aravind SR, Krishnan LK. Curcumin-albumin conjugates as an effective anti-cancer agent with immunomodulatory properties. Int Immunopharmacol. 2016 May;34:78-85. [Google Scholar]
- 9.Ashraf A, Ashraf MM, Rafiqe A, Aslam B, Galani S, Zafar S, Asad F, Asghar RD, Akram S, Ahmed H, Shah SMA, Asif R. In vivo antiviral potential of Glycyrrhiza glabra extract against Newcastle disease virus. Pak J Pharm Sci. 2017 Mar;30(2(Suppl.)):567-572. [Google Scholar]
- 10.Pastorino G, Cornara L, Soares S, Rodrigues F, Oliveira MBPP. Liquorice (Glycyrrhiza glabra): A phytochemical and pharmacological review. Phytother Res. 2018 Dec;32(12):2323-2339. [Google Scholar]
- 11.Hejazi II, Beg MA, Imam MA, Athar F, Islam A. Glossary of phytoconstituents: Can these be repurposed against SARS CoV-2? A quick in silico screening of various phytoconstituents from plant Glycyrrhiza glabra with SARS CoV-2 main protease. Food Chem Toxicol. 2021 Apr;150:112057. [Google Scholar]
- 12.Vafaei F, Abdollahzadeh F. Investigating the effects of Hydroalcoholic extract of jujube fruit (Zizyphus vulgaris L.) on second degree burn wound healing in Balb/c mice. J Med Life. 2015;8(Spec Iss 2):117-120. [Google Scholar]
- 13.Arshad N, Mehreen A, Liaqat I, Arshad M, Afrasiab H. In vivo screening and evaluation of four herbs against MRSA infections. BMC Complement Altern Med. 2017 Nov 23;17(1):498. [Google Scholar]
- 14.Vohora SB, Naqvi SA, Kumar I. Antipyretic, analgesic and antimicrobial studies on Sisymbrium irio. Planta Med. 1980 Mar;38(3):255-9. [Google Scholar]
- 15.Mickymaray S. One-step Synthesis of Silver Nanoparticles Using Saudi Arabian Desert Seasonal Plant Sisymbrium irio and Antibacterial Activity Against Multidrug-Resistant Bacterial Strains. Biomolecules. 2019 Oct 28;9(11):662. [Google Scholar]
- 16.Abu-Qaoud H, Shawarb N, Hussen F, Jaradat N, Shtaya M. Report: Comparison of qualitative, quantitative analysis and antioxidant potential between wild and cultivated Borago officinalis leaves from palestine. Pak J Pharm Sci. 2018 May;31(3):953-959. [Google Scholar]
- 17.Leos-Rivas C, Verde-Star MJ, Torres LO, Oranday-Cardenas A, Rivas-Morales C, Barron-Gonzalez MP, Morales-Vallarta MR, Cruz-Vega DE. In vitro amoebicidal activity of borage (Borago officinalis) extract on Entamoeba histolytica. J Med Food. 2011 Jul-Aug;14(7-8):866-9. [Google Scholar]
- 18.Yatoo MI, Gopalakrishnan A, Saxena A, Parray OR, Tufani NA, Chakraborty S, Tiwari R, Dhama K, Iqbal HMN. Anti-Inflammatory Drugs and Herbs with Special Emphasis on Herbal Medicines for Countering Inflammatory Diseases and Disorders – A Review. Recent Pat Inflamm Allergy Drug Discov. 2018;12(1):39- 58. [Google Scholar]
- 19.Sutovska M, Capek P, Franova S, Joskova M, Sutovsky J, Marcinek J, Kalman M. Antitussive activity of Althaea officinalis L. polysaccharide rhamnogalacturonan and its changes in guinea pigs with ovalbumine-induced airways inflammation. Bratisl Lek Listy. 2011;112(12):670-5. [Google Scholar]
- 20.Hage-Sleiman R, Mroueh M, Daher CF. Pharmacological evaluation of aqueous extract of Althaea officinalis flower grown in Lebanon. Pharm Biol. 2011 Mar;49(3):327-33. [Google Scholar]
- 21.Zaghlool SS, Abo-Seif AA, Rabeh MA, Abdelmohsen UR, Messiha BAS. Gastro-Protective and Anti-Oxidant Potential of Althaea officinalis and Solanum nigrum on Pyloric Ligation/Indomethacin-Induced Ulceration in Rats. Antioxidants (Basel). 2019 Oct 25;8(11):512. [Google Scholar]
- 22.Benso B, Rosalen PL, Pasetto S, Marquezin MCS, Freitas-Blanco V, Murata RM. Malva sylvestris derivatives as inhibitors of HIV-1 BaL infection. Nat Prod Res. 2021 Mar;35(6):1064-1069. [Google Scholar]
- 23.Samavati V, Manoochehrizade A. Polysaccharide extraction from Malva sylvestris and its anti-oxidant activity. Int J Biol Macromol. 2013 Sep;60:427-36. [Google Scholar]
- 24.Arshad N, Mehreen A, Liaqat I, Arshad M, Afrasiab H. In vivo screening and evaluation of four herbs against MRSA infections. BMC Complement Altern Med. 2017 Nov 23;17(1):498. [Google Scholar]
- 25.Mehreen A, Waheed M, Liaqat I, Arshad N. Phytochemical, Antimicrobial, and Toxicological Evaluation of Traditional Herbs Used to Treat Sore Throat. Biomed Res Int. 2016;2016:8503426. [Google Scholar]
- 26.Gheware A, Dholakia D, Kannan S, Panda L, Rani R, Pattnaik BR, Jain V, Parekh Y, Enayathullah MG, Bokara KK, Subramanian V, Mukerji M, Agrawal A, Prasher B. Adhatoda Vasica attenuates inflammatory and hypoxic responses in preclinical mouse models: potential for repurposing in COVID-19-like conditions. Respir Res. 2021 Apr 6;22(1):99. [Google Scholar]
- 27.Khan N, Qadir A, Warsi MH, Ali A, Tahir A, Ali A. Identification of the Phytoconstituents in Methanolic Extract of Adhatoda vasica L. Leaves by GC-MS Analysis and its Antioxidant Activity. J AOAC Int. 2021 Aug 30:qsab113. [Google Scholar]