Sanative effect of a low-cost Novel Green Formulation – IM-SSS20 to minimize the inflammatory and cytokine storm against Respiratory Diseases
Abstract
Objective: To develop a herbal formulation combining four ingredients namely Ocimum sanctum, Green tea, Nyctanthes arbor-tristis and  Hygrophila auriculata  to combat infections that affect the respiratory system leading to inflammation, stress and other complications.Method: The management of respiratory conditions was tried with the low cost multi herbal preparation IM-SSS 20.We have developed a herbal formulation combining four ingredients namely Ocimum sanctum, Green tea, Nyctanthes arbor-tristis  and  Hygrophila auriculata. Plant secondary metabolites in the developed multi-herbal formulation (MHF) (IM-SSS-20) were detected through quantitative analysis. Anti-bacterial and anti-fungal activity of the IM-SSS-20 were also determined. In-vitro clinical study was done to measure the haematological parameters like Haemoglobin (Hb), Haematocrit (PCV), Total RBC (RBC) and Total WBC (TC)  and estimate the expression of several biomarkers like IL-6, IL-8, IL-10 and TNF-α.Results:The phytochemicals like triterpenes, flavonoids, saponins, and tannins were abundantly found in the IMSSS-20 extract. The inhibitory action of IM-SSS20 was dose-dependent and significant anti-bacterial activity was seen in the case of Escherichia coli followed by Streptococcus aureus and Klebsiella pneumonia respectively. The IM-SSS 20 also showed antifungal activity, the activity was maximum in case of C. albicans and was least for A.niger. In this study we observed a lower value of hemoglobin, hematocrit, total RBC and total WBC in respiratory infected patients. IM-SSS20 was effective in normalizing the concentration of Hb, PCV, RBC and TC. Conclusion: The multi-herbal formulation IM-SSS20 showed promising results in-vitro studies and further studies are required to explore its efficacy in humans. This low-cost formulation can improve health as well as economy of the developing countries.KEYWORDS: Respiratory diseases, Ocimum sanctum, Green tea, Nyctanthes arbor-tristis  and  Hygrophila auriculata.References
Forum of International Respiratory Societies (FIRS). Respiratory diseases in the world: realities of today—opportunities for tomorrow [Internet]. Sheffield (UK): European Respiratory Society; 2013 [accessed 20 Nov 2013]. Available from: http://www.thoracic.org/ global-health/firs-report-respiratory-diseases-in-the-world/ index.php
R.Lozano,M.Naghavi,K.Foremanetal.,"Global and regional mortality from 235 causes of death for 20 age groups in 1990 and2010:asystematicanalysisfortheGlobalBurdenofDisease Study2010,"TheLancet,vol.380,pp.2095–2128,2012
Hay, S. I. et al. Global, regional, and national disability-adjusted life-years (DALYs) for 333 diseases and injuries and healthy life expectancy (HALE) for 195 countries and territories, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016. Lancet390, 1260–1344 (2017)
BTS, "The burden of lung disease: a statistical report from theBritishThoracicSociety,"2nded.,British Thoracic Society, London, UK, 2006, http://www.brit-thoracic.org.uk/deliveryof-respiratory-care/burden-of-lung-disease-reports.aspx.
R.Hubbard,"Theburdenoflungdisease,"Thorax,vol.61,no.7, pp.557–558,2006.
R. Loddenkemper, G. J. Gibson, and Y. Sibille, "Respiratory health and disease in Europe: the new European Lung White Book,"European Respiratory Journal,Vol.42,pp.559–563,2013.
D.E.Schraufnagel,F.Blasi,M.Kraft,M.Gaga,P.Finn,andK. F. Rabe, "An official American Thoracic Society and European RespiratorySocietypolicystatement:disparities in respiratory health,"EuropeanRespiratoryJournal,vol.42,pp.906–915,2013.
Septimus EJ, Albrecht HH, Solomon G, Shea T, Guenin EP.Extended-Release Guaifenesin/Pseudoephedrine Hydrochloride for Symptom Relief in Support of a Wait-and-See Approach for the Treatment of Acute Upper Respiratory Tract Infections: A Randomized, Double-Blind, Placebo-Controlled Study. Curr Ther Res Clin Exp. 2017; 84: 54-61.
Shapiro D, Bodinayake CK, Nagahawatte A, Devasiri V, Kurukulasooriya R, Hsiang J, Nicholson B, De Silva AD, Østbye T, Reller ME, Woods CW, Tillekeratne LG. Burden and Seasonality of Viral Acute Respiratory Tract Infections among Outpatients in Southern Sri Lanka. Am J Trop Med Hyg. 2017; 97(1):88-96
Siafakas N, Vermeire P, Pride P, et al. Optimal assessment and management of chronic obstructive pulmonary disease (COPD). Eur Respir J 1995; 8: 1398–1320.
George J, Ioannides DLL, Santamaria NM, Kong DC, Stewart K. Use of complementary and alternative medicines by patients with chronic obstructive pulmonary disease. Med J Aust 2004; 181: 248–251.
Anne Pernille Toft-Petersen, Christian Torp-Pedersen, Ulla Møller Weinreich, Bodil Steen Rasmussen Association between hemoglobin and prognosis in patients admitted to hospital for COPD Int J Chron Obstruct Pulmon Dis. 2016; 11: 2813–2820. Published online 2016 Nov 10. doi: 10.2147/COPD.S116269.
Seon Cheol Park, Young Sam Kim, Young Ae Kang, Eun Cheol Park, Cheung Soo Shin, Dong Wook Kim, Chin Kook Rhee Hemoglobin and mortality in patients with COPD: a nationwide population-based cohort stud,yInt J Chron Obstruct Pulmon Dis. 2018; 13: 1599–1605. Published online 2018 May 16. doi: 10.2147/COPD.S159249
Ernst E. Complementary therapies in asthma: what patients use. J Asthma 1998;35:667–71.
Hnizdo E, Singh T, Churchyard G. Chronic pulmonary function impairment caused by initial and recurrent pulmonary tuberculosis following treatment. Thorax 2000; 55: 32–38.
Plit ML, Anderson R, Van Rensburg CE, et al. Influence of antimicrobial chemotherapy on spirometric parameters and pro-inflammatory indices in severe pulmonary tuberculosis. Eur Respir J 1998; 12: 351–356.
Ross J, Ehrlich RI, Hnizdo E, et al. Excess lung function decline in gold miners following pulmonary tuberculosis. Thorax 2010; 65: 1010–1015.
Pasipanodya JG, Miller TL, Vecino M, et al. Pulmonary impairment after tuberculosis. Chest 2007; 131: 1817–1824.
Pasipanodya JG, McNabb SJ, Hilsenrath P, et al. Pulmonary impairment after tuberculosis and its contribution to TB burden. BMC Public Health 2010; 10: 259.
Maguire GP, Anstey NM, Ardian M, et al. Pulmonary tuberculosis, impaired lung function, disability and quality of life in a high-burden setting. Int J Tuberc Lung Dis 2009; 13: 1500–1506.
Ralph AP, Kenangalem E, Waramori G, et al. High morbidity during treatment and residual pulmonary disability in pulmonary tuberculosis: under-recognised phenomena. PLoS One 2013; 8: e80302.
Schunemann HJ, Dorn J, Grant BJ, et al. Pulmonary function is a long-term predictor of mortality in the general population: 29-year follow-up of the Buffalo Health Study. Chest 2000; 118: 656–664
Medicinal Plants and Ayurvedic Herbal Medicines. AYURVEDA: National Institute of Ayurvedic Medicine URL: http://niam.com/corp-web/mediplnt.html
Kritkar KR, Basu BD, LM Basu. Indian Medicinal Plant 1993; 2: 1526-1528
Wealth of India, A Dictionary of Indian Raw Materials and Industrial Products, National Institute of Science Communication, CSIR, New Delhi 1997; 8: 69-70.
Hiremath V, Hiremath B. S, Mohapatra S, Das A. K. Literary Review of Parijata (Nyctanthus Arbor-Tristis Linn.) An Herbal Medicament with Special Reference to Ayurveda and Botanical Literatures. Biomed Pharmacol J 2016;9(3)
Singh N, Hoette Y, Miller R. Tulsi: The Mother Medicine of Nature. 2nd ed. Lucknow: International Institute of Herbal Medicine; 2010. p. 28‑47.
Kumar A, Rahal A, Chakraborty S, Tiwari R, Latheef SK, Dhama K. Ocimum sanctum (Tulsi): a miracle herb and boon to medical science– A Review. International Journal of Agronomy and Plant Production 2013; 4 (7):1580-1589.
Manikandan P, Murugan RS, Abbas H, Abraham SK, Nagini S. Ocimum sanctum Linn. (Holy Basil) ethanolic leaf extract protects against 7,12‑dimethylbenz (a) anthracene-induced genotoxicity, oxidative stress, and imbalance in xenobiotic-metabolizing enzymes. J Med Food 2007;10:495‑502.
Siddique YH, Ara G, Beg T, Afzal M. Anti-genotoxic effect of Ocimum sanctum L. extract against cyproterone acetate induced genotoxic damage in cultured mammalian cells. Acta Biol Hung 2007;58:397‑409.
Gupta SK, Prakash J, Srivastava S. Validation of claim of Tulsi, Ocimum sanctum Linn as a medicinal plant. Ind. J. Experimental Biol 2002; 40:765-773.
Govind P. An overview of anticancer natural products. J. Pharm. Res 2009; 2(12):1799-1803.
Kumar A, Rahal A, Verma AK. In vitro antibacterial activity of hot aqueous extract (HAE) of Ocimum sanctum (Tulsi) leaves. Ind. J. Vety. Medicine 2011b; 31(2):96-97
Nadkarni K, Nadkarni A: Indian Materia Medica with Ayurvedic, UnaniTibbi, Siddha, Allopathic, Homeopathic, Naturopathic & Home Remedies, 2 vol. Popular Prakashan Private Ltd, Bombay, India 1982:1999.
Banerjee S, Prashar R, Kumar A, Rao A: Modulatory influence of alcoholic extract of Ocimum leaves on carcinogenâ€metabolizing enzyme activities and reduced glutathione levels in mouse. 1996.
Vasudevan P, Kashyap S, Sharma S. Bioactive botanicals from basil (Ocimum sp.). J Sci Ind Res (C) 1999;58:332-8
Mondal S, Varma S, Bamola VD, Naik SN, Mirdha BR, Padhi MM, et al. Double-blinded randomized controlled trial for immunomodulatory effects of Tulsi (Ocimum sanctum Linn.) leaf extract on healthy volunteers. J Ethnopharmacol 2011;136:452-6
Bhattacharyya D, Sur TK, Jana U, Debnath PK. Controlled programmed trial of Ocimum sanctum leaf on generalized anxiety disorders. Nepal Med Coll J 2008;10:176‑9
Kothari S, Bhattacharya A, Ramesh S, Garg S, Khanuja S: Volatile constituents in oil from different plant parts of methyl eugenol-rich Ocimum tenuiflorum Lf (syn. O. sanctum L.) grown in South India. Journal of Essential Oil Research 2005, 17(6):656-658.
Parrotta JA: Healing plants of peninsular India: CABI publishing; 2001
Wangcharoen W, Morasuk W. Antioxidant capacity and phenolic content of holy basil. Songklanakarin J Sci Technol 2007;29:1407‑15
Wagner H, Norr H, Winterhoff H. Plant adaptogens. Phytomed 1994; 1:63-76
Aswar MK, Joshi RH. Anti-Cataleptic Activity of Various Extracts of Ocimum sanctum. Int. J. Pharma. Res. Development–Online IJPRD. 2(1). Ref No. IJPRD/2010/PUB/ARTI/VOL-2/ISSUE6/AUG/015; 2010.
Graham, H.N. Green tea composition, consumption, and polyphenol chemistry. Prev. Med. 1992, 21, 334–350.
Miura, Y., Chiba, T., & Tomita, I. (2001). Tea catechins prevent the development of atherosclerosis in apoprotein E-deficient mice. Journal of Nutrition, 131, 27–32.
Beltz, L. A., Bayer, D. K., Moss, A. L., & Simet, I. M. (2006). Mechanisms of cancer prevention by green and black tea polyphenols. Anticancer Agents in Medicinal Chemistry, 6(5), 389–
Matsuyama, T., Tanaka, Y., Kamimaki, I., Nagao, T., & Tokimitsu, I. (2008). Catechin safely improved higher levels of fatness, blood pressure, and cholesterol in children. Obesity (Silver Spring), 16(6), 1338–1348.
Kris-Etherton, P. M., Hecker, K. D., & Bonanome, A. (2002). Bioactive compounds in foods: Their role in the prevention of cardiovascular disease and cancer. WCRF/ AICR expert report, food, nutrition, physical activity and the prevention of cancer: A global perspective. American Journal of Medicine, 113(9B), 71S–88S.
Song, J. M., & Seong, B. L. (2007). Tea catechins as a potential alternative anti-infectious agent. Expert Review of Anti-infective Therapy, 5, 497.
The benefits of green tea. Available from: <http://www.coffee-
tea-pots-cups.net/ tea/green> (accessed on 15.09.2008).
Yamamoto, T.; Juneja, L.R.; Chu, D.; Kim, M. Chemistry and Applications of Green Tea; CRC Press: Boca Raton, FL, USA, 1997; pp. 6–34.
Frei, B., & Higdon, J. V. (2003). Antioxidant activity of tea polyphenols in vivo: Evidence from animal studies. Journal of Nutrition, 133(10), 3275S–3284S.
http://www.gaiaresearch.co.za/greentea.html
Girach RD, Aminuddin SA, Siddiqui PA, Khan SA. Ethnomedicinal studies on Harsinghar (Nyctanthes arbortristis L)- A less known medicinal plant in Unani medicine. Hamdard Medicines 1994; 37: 60
Mahida Y, Mohan JSS. Screening of plants for their potential antibacterial activity against Staphylococcus and Salmonella sp. Natural Product Radiance 2007; 6: 301-305.
Das S, Sasmal D, Basu SP. Antispasmodic and antihelmintic activity of Nyctanthes arbortristis Linn. International Journal of Pharmaceutical Science and Research 2010; 1: 51-55.
Singh A, Malhotra S, Subban R. Anti-inflammatory and analgesic agents from Indian Medicinal Plants. International Journal of Integrative Biology 2008; 3: 5772.
Das S, Sasmal D, Basu SP. Anti-inflammatory and antinociceptive activity of arbortristoside-A. Journal of Ethnopharmacology 2008; 116: 198-203.
Rathee JS, Hassarajani SA. Antioxidant activity of Nyctanthes arbortristis leaf extract. Food Chemistry 2007; 103: 1350-1357.
Choudhary M, Raghuwansi A. Nyctanthes arbortristis - A Immunostimulant. National Conference on "Recent Advances in Herbal Drug Technology." Organized by: Lakshmi Narain College of Pharmacy, Bhopal.
Rathod N, Raghuveer I, Chitme HR, Chandra R. Free Radical scavenging activity of Nyctanthes arbortristis in streptozotocin-induced diabetic rats. Indian Journal of Pharmaceutical Educational Research 2010; 4: 288-294.
Narendhirakannan RT, Smeera T. In-vitro antioxidant studies on ethanolic extracts of leaves and stems of Nyctanthes arbortristis L. (Night-flowering jasmine). International Journal of Biology and Medical Research 2010; 1: 188- 192.
Suresh V, Arunachalam G, Senthil KN. In-vitro anthelmintic activity of Nyctanthes arbortristis bark. Journal of Pharmaceutical Research 2011; 4: 283-284.
Nair R, Kalariya T, Chanda S. Antibacterial activity of some selected Indian Medicinal Flora. Turkish Journal of Biology 2005; 29: 41-47.
Sasmal D, Das S, Basu SP. Phytoconstituents and therapeutic potential of Nyctanthes arbortristis. Pharmacognosy Reviews 2007; 1: 344-349.
Taylor JLS, Rabe T, McGaw LJ, Jager AK, Staden VJ. Towards the scientific validation of traditional medicinal plants. Plant Growth Regulation, 2001, 34(1): 23-37.
Mukherjee PK, Maiti K, Mukherjee K, Houghton PJ. Leads from Indian medicinal plants with hypoglycemic potentials. J. Ethnopharmacol, 2006, 106(1), 1-28.
Mukherjee PK, Kumar V, Mal M, Houghton PJ. Acetyl cholinesterase inhibitors from plants. Phytomedicine, 2007, 14(4), 289-300.
Anubha Singh and Handa SS. Hepatoprotective activity of Apium graveolens ana Hygrophila auriculata against paracetamol and thioacetamide intoxication in rats. J Ethanopharmacol, 1995, 49(3): 119-126
P. Shanmugasundaram and S. Venkataraman, "Hepatoprotective and antioxidant effects of Hygrophila auriculata (K. Schum) Heine Acanthaceae root extract," Journal of Ethnopharmacology, vol. 104, no. 1-2, pp. 124–128, 2006.
Patra A, Murthy NP, Jha S. Pharmacognostical standardization of leaves of Hygrophila spinosa T. Anders Phcog J. 2009;1:82–7.
Md. Sarfaraj Hussain SheebaFareed &MohammadAli Hyphenated chromatographic analysis of bioactive gallic acid and quercetin in Hygrophila auriculata (K. Schum) Heine growing wildly in marshy places in India by validated HPTLC method, Asian Pacific Journal of Tropical Biomedicine 2 (2) Supplement, Feb 2012, Pages S477-S483
A. Gomes, Manika Das & S.C Dasgupta " Haemanitic effect of hygrophilla spinasa T, Anderson on experimental rodents" Indian journal of Experimental Biology Vol. 39, april 2001,pp. 381-382.
Chitralekha Mukherjee Santa Datta (De), Estimation of Micronutrients in Fresh Kulekhara Leaves (Hygrophilla auriculata), International Journal of Science and Research Volume 6 ( 2), February 2017, 838-40
B. Srilakhsmi, Nutrition Science, New Age publications.
A Adhikari, S Darbar, T Chatterjee, M Das, N Polley, M Bhattacharyya, Spectroscopic Studies on Dual Role of Natural Flavonoids in Detoxification of Lead Poisoning: Bench-to-Bedside Preclinical Trial. ACS Omega 2018, 3 (11), 15975–15987 (first and second author have equal contribution)
Evans WC. Trease & Evans Pharmacognosy. 15th ed. Amsterdam: Elsevier; 2002. pp. 135-49.
Guevarra BQ. A guide book to Plant Screening: Phytochemical and biological. Manila: Research Center for the Natural Sciences, UST Publishing House; 2005. pp. 63-99
Marigo G. Méthode de fractionnement et d'estimation des composés phénoliques chez les végétaux. Phytochemical analysis 1973: 59: 106-110.
Emmanuel Talla, Alfred Ngenge Tamfu, Pierre Biyanzi, Paul Sakava, Forche Peter Asobo, Joseph Tanyi Mbafor, Nestor Fernand Fohouo Tchuenguem, Robert Ndjouenkeu. Phytochemical screening, antioxidant activity, total polyphenols and flavonoids content of different extracts of propolis from Tekel (Ngaoundal, Adamawa region, Cameroon). The Journal of Phytopharmacology 2014; 3(5): 321-329.
Brand-Williams W., Cuvelier M. E., Berset C. Use of free radical method to evaluate antioxidant activity. Lebensm. Wiss. Technol 1995: 28: 25–30.
Erica W. T., Dejair M., Giuseppina N., & Antonio S. Paulo C. S., Seasonal Variation, Chemical Composition and Antioxidant activity of Brazilian Propolis Samples. eCAM 2008: 7(3): 307–315
Gülçin I., Elias R., Gepdiremen A., Chea A. & Topal F. , Antioxidant activity of bisbenzyl isoquinoline alkaloids from Stephania rotunda: cepharanthine and fangchinoline. Journal of Enzymatic Inhibition and Medical Chemistry 2010: 25: 44–53.
Mihai C. M., Liviu A. M., Daniel S. D., Lavinia B. Correlation between Polyphenolic Profile and Antioxidant Activity of Propolis from Transylvania. Animal Science and Biotechnologies 2011:44 (2): 100-103.
Abdullahi M. I., Iliya I., Haruna A. K., Sule M. I., Musa A. M. & Abdullahi M. S. Preliminary phytochemical and antimicrobial investigations of leaf extracts of Ochna schweinfurthiana (Ochnaceae). African Journal of Pharmacy and Pharmacology, 2010: 4(2): 083-086
Srimoyee Saha, S. Das, R. Basu "Green Synthesis Of Copper Oxide - Tinospora cordifolia Nanoparticle: Antioxidant And Antimicrobial Activity" ejpmr, 2019,6(7), 340-346.
Srimoyee Saha, S. Das, R. Basu "Green Synthesis Of Copper Oxide - Tinospora cordifolia Nanoparticle: Antioxidant And Antimicrobial Activity" EJPMR 2019,6(7), 340-346.
S Darbar, S Saha, K Pramanik, A Chattopadhyay. Preliminary Assessment of Acute and 28-Day Repeated Dose Oral Toxicity of a Newly Developed Herbal Mixture on Experimental Animal. Indian Journal of Pharmaceutical education and Research 2000; 54 (1), 135-142
Ji Hye Han, Jung Heun Ju, Yong Sun Lee, Ju Ho Park, In Jun Yeo, Mi Hee Park, Yoon Seok Roh, Sang Bae Han & Jin Tae Hong. Astaxanthin alleviated ethanolinduced liver injury by inhibition of oxidative stress and inflammatory responses via blocking of STAT3 activity. Scientific RePoRTS | (2018) 8:14090 | DOI:10.1038/s41598-018-3249
Compean KL, Ynalvez RA. Antimicrobial activity of plant secondary metabolites: A review. Res J Med Plant 2014;8:204-13.
Wink M. Modes of action of herbal medicines and plant secondary metabolites. Medicines (Basel) 2015;2:251-86.
Cushnie TP, Cushnie B, Lamb AJ. Alkaloids: An overview of their antibacterial, antibiotic-enhancing and antivirulence activities. Int J Antimicrob Agents 2014;44:377-86.
Kavitaa K, Singha VK, Jha B. 24-Branched Δ5 sterols from Laurencia papillosa red seaweed with antibacterial activity against human pathogenic bacteria. Microbiol Res 2014;169:301-6.
Cushnie TP, Lamb AJ. Antimicrobial activity of flavonoids. Int J Antimicrob Agents 2005;26:343-56.
Scalbert A. Antimicrobial properties of tannins. Phytochemistry 1991;30:3875-83.
Akinpelu BA, Igbeneghu OA, Awotunde AI, Iwalewa EO, Oyedapo OO. Antioxidant and antibacterial activities of saponin fractions of Erythrophleum suaveolens (Guill. And Perri.) stem bark extract. Scientific Research and Essays 2014;9:826-33.
Kouam J, Mabeku LBK, Kuiate JR, Tiabou AT, Fomum ZT. Antimicrobial glycosides and derivatives from roots of Picralima nitida. Int J Chem 2011;3:2011.
Mokoka TA, McGaw LJ, Mdee LK, Bagla VP, Iwalewa EO, Eloff JN. Antimicrobial activity and cytotoxicity of triterpenes isolated from leaves of Maytenus undata (Celastraceae). BMC Complement Altern Med 2013;13:111.
Erica W. T., Dejair M., Giuseppina N., & Antonio S. Paulo C. S., Seasonal Variation, Chemical Composition and Antioxidant activity of Brazilian Propolis Samples. eCAM 2008: 7(3): 307–315
Mihai C. M., Liviu A. M., Daniel S. D., Lavinia B. Correlation between Polyphenolic Profile and Antioxidant Activity of Propolis from Transylvania. Animal Science and Biotechnologies 2011:44 (2): 100-103.
Chang C. C., Ming M. H., Wen H. M. & CHern J. C. Estimation of total flavonoid content in propolis bytwo complementary colorimetric methods. Journal of Food and Drug Analysis 2002: 10: 178–182. 3): 307–315
Kujumgiev A., Tsvetkova I., Serkedjieva Y., Christov R. & Popova S. Antibacterial, antifungal andantiviral activity of propolis of different geographic origin. Journal of Ethnopharmacology 1999: 64: 235-240.
Bulletin of the World Health Organization (1993) Research guidelines for evaluating the safety and efficacy of herbal medicine 1-86.
Akerele O (1993) Summary of WHO guidelines for the assessment of herbal Medicines.HerbalGram28: 13-19.
Ren G, Hu D, Cheng EW, Vargas-Reus MA, Reip P, Allaker RP. Characterization of copper oxide nano particles for antimicrobial applications. Int J Antimicrob Agents, 2009; 33(6): 587-590.
Sankar R, Manikandan P, Malarvizhi V, Fathima T, Shivashangari KS, Ravikumar V. Green synthesis of colloidal copper oxide nanoparticles using Carica papaya and its application in photocatalytic dye degradation. Spectrochim Acta Mol Biomol Spectrosc, 2014; 121: 746-750.
Sergei P. Atamas, Svetlana P. Chapoval and Achsah D. Keegan. Cytokines in chronic respiratory diseases. F1000 Biology Reports 2013, 5:3; 1-12
William J. Branchett and Clare M. Lloyd. Regulatory cytokine function in the respiratory tract Mucosal Immunology (2019) 12:589 – 600
Iwasaki, A. & Pillai, P. S. Innate immunity to influenza virus infection. Nat. Rev. Immunol. 14, 315–328 (2014).
Lloyd, C. M. & Hawrylowicz, C. M. Regulatory T cells in asthma. Immunity 31,438–449 (2009).
Ordonez CL, Shaughnessy TE, Matthay MA, Fahy JV: Increased neutrophil numbers and IL-8 levels in airway secretions in acute severe asthma: Clinical and biologic significance. American journal of respiratory and critical care medicine 2000, 161:1185-90.
Redhu NS, Gounni AS: Function and mechanisms of TSLP/TSLPR complex in asthma and COPD. Clin Exp Allergy 2012, 42:994-1005.
Keatings VM, Collins PD, Scott DM, Barnes PJ: Differences in interleukin-8 and tumor necrosis factor-alpha in induced sputum from patients with chronic obstructive pulmonary disease or asthma. American journal of respiratory and critical care medicine 1996, 153:530-4.
Sarkar M, Rajta PN, Khatana J. Anemia in Chronic obstructive pulmonary disease: Prevalence, pathogenesis, and potential impact. Lung India. 2015;32(2):142-151.
Vestbo J, Hurd SS, Agusti AG, Jones PW, Vogelmeier C, Anzueto A, et al. Global strategy for the diagnosis, management, and prevention of chronic obstructive pulmonary disease: GOLD executive summary. Am J RespirCrit Care Med. 2013;187:347–65.
Boutou AK, Stanopoulos I, Pitsiou GG, Kontakiotis T, Kyriazis G, Sichletidis L, et al. Anemia of chronicdiseasein chronic obstructive pulmonarydisease: A case-control study of cardiopulmonary exercise responses. Respiration. 2011;82:237–45.
Attaran D, Khajedalouee M, Ahmadi F, Rezaeitalab F, Towhidi M, Asnaashari A, et al. Anemia in COPD patients and its relation to serum levels of erythropoietin. Tanaffos. 2009;8:11–6.
Sangita Agarwal, Srimoyee Saha, Tathagata Deb and Soumendra Darbar, "Immunity augmenting food supplements for susceptible individuals in combating pandemic COVID-19 (Review)", Parana Journal of Science and Education. Vol. 6, No. 4, 2020, pp. 79-88. https://doi.org/10.5281/zenodo.3880638
