Sohag University Sohag Medical Journal Faculty of Medicine Saussurea costus may help in the treatment of COVID-19 Mahmoud Saif-Al-Islam Tropical Medicine and Gastroenterology Department, Sohag University Hospital, Faculty of Medicine, Egypt. Abstract Coronavirus disease 2019 (COVID-19) is an emerging disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that causing an ongoing pandemic and is considered as a national public health emergency. The signs and symptoms of COVID-19 vary from mild symptoms to a fulminating disease with acute respiratory distress syndrome (ARDS) and multi-organ failure, which may culminate into death with no available vaccines or specific antiviral treatments. God provides us with important medicinal plants. Here I shall shed the light on one of these plants that may help in the treatment of COVID-19 or may even cure it. Saussurea costus (S. costus) is a popular plant with medical importance, the roots of which are widely used for healing purposes throughout human history with great safety and effectiveness. Previous studies revealed the presence of many bioactive phytochemical molecules that has antiseptic, antibacterial, antifungal, antiviral, anti- inflammatory, antioxidant, anti-lipid peroxidation, immunostimulant, immunom- odulating, analgesic, bronchodilor, hepatoprotective and antihepatotoxic properties. S. Costus has immunomodulatory effects on cytokine release and has complement- inhibitor substances helpful in the treatment of some diseases related to marked activation of the complement system, like respiratory distress. Keywords: Saussurea costus, COVID-19, respiratory distress. Background: S. costus (synonymous with widely investigated6. Various compo- Saussurea lappa), belongs to family unds isolated from the plant have Asteraceae, widely distributed in diff- medicinal properties including terp- erent regions in the world; however, enes, alkaloids, anthraquinones, and numerous species are found in India1, favonoids. The plant has many terpe- in Pakistan, and some parts of nes with anti-inflammatory and antitu- Himalayas2. The plant is well-known mor properties, such as costunolide, about 2500 years ago. It is used in dihydrocostunolide, 12-methoxydihy- different ancient systems of medicine drocostunolide, dehydrocostus lactone, such as Ayurveda, Unani, and Siddha3. dihydrocostus lactone7,α-hydroxydeh- S. costus is well Known in Islamic ydrocostus lactone, β-hydroxydehy- medicine, which enlisted in the Holy drocostus lactone, lappadilactone8, Ahadith said by Prophet Muhammad betulinic acid, betulinic acid methyl (Peace be upon him). It is known in ester, mokko lactone9, reynosin, Arab countries as Al-Kost Al-Hindi4, santamarine, cynar-opicrin10, saussur- Al-Kust, and Al-Qust5, and used by eamines A-C11, alantolactone, isoalan- traditional healers since the era of tolactone, α-cycloco-stunolide12, β- Islamic civilization4. cyclocostunolide, isodihydro- In scientific literature, the biological costunolide13, 1β-hydroxy arbusculin activities of the roots of S. costus are A9, arbusculin B6. Also, it contains 6 SOHAG MEDICAL JOURNAL Saussurea costus may help in the treatment of COVID-19 Vol. 24 No. 3 July 2020 Mahmoud Saif-Al-Islam pregnenolone, β-sitosterol, daucosterol, ensin converting enzyme (ACE) 12-octadecadienoic acid14, costic acid, inhibitor (myrcene15), diuretic myrcene, p-cymene, tannin, caryophy- (friedelin15), antiedemic(caryophylline llene-oxide, octanoic acid, stigma- oxide, lupeol, taraxasterol15), antirhe- asterol, lupeol,botulin, caryophyllene, umatic (lupeol15), antidermatitis (cary- palmitic acid, oleic acid, inulin, camp- ophyllene15), anticancer3,13,24,27,39,47,51-55 hene, alphaphellandrene, hexanoic (caryophyllene oxide, caryophyllene, acid, saussurine, acetic acid, beta- costunolide, lupeol, tannin, betulin15), ionone, friedelin, taraxasterol15, and sedating16, and anticonvulsant many other constituents14,15. properties3,23,27,28,56 (myrcene15). S.costus has antiseptic16, antibacterial S. costus is used to treat, fever, head- 17,18(costicacid,dehydrocotuslactone,m ache, pain, cough, bronchial asth- yrcene,pcymene, tannin15), antif- ma16,28,57-59, bacterial infections17, dia- ungal19,20 (caryophylleneoxide, myrc- rrhea23, cholera57,59, typhoid23,24, tube- ene, octanoicacid,pcymene15), antiv- rculosis, leprosy23,24,27, vomiting, dysp- iral3,17,21-25(p-cymene,stigmasterol, epsia23,28, hiccups27, gastric tannin15), antiflu (lupeol, p-cymene15), ulcer3,23,43,44,60,61, abdominal pain23,28, anti-Epstein-barr virus(lupeol, diarrhea23, tenesmus23, arthritis3,24, rhe- betulin15), antinematodal23,26, anthe- umatoid arthritis, systemic lupus ery- lmintic23,27,28 (tannin15), anti-trypan0- themaatosus, respiratory distress41, osoma6,anti-malarial23,27 (lupeol15), chronic skin diseases57,59, itching28, anti-leishmanic (caryophyllene15), scabies, ringworm, bruises, cuts28,62,63, antiinflammatory23,29-35, antioxidant36,37 and diabetes mellitus50. (myrcene, palmitic acid, stigmasterol, tannin15), anti-lipid peroxidation37, COVID-19 antileukotriene-D4 (oleic acid15), COVID-19 has emerged as a pandemic immunostimulant37,38 (inulin15), and a public health crisis. The immunomodulating23,39-41, causative agent was named SARS- analgesic27,28,35 (myrcene, p-cymene15), CoV-2 and was detected from throat antipyretic(beta-sitosterol15), swab samples64. It enters the cells by bronchodilating16 (caryophyllene15), endocytosis after attachment to the expectorant (camphene, inulin, alpha- angiotensin-converting enzyme-2 phellandrene, caryophyllene, hexanoic (ACE2) receptors on cells in the lung, acid15), gastic cytoprotective42-45 gastrointestinal tract, blood vessels, (caryophyllene15), antiulcer (tannin15), heart, and kidney65. Many countries try choleretic (oleic acid15), cholagogic46, to find a cure or vaccine to this disease. carminative16,28,antispasmodic23,47 Clinical features of COVID-19 include (myrcene,saussurine15), tiredness, fever, dry cough, shortness antidiarrheal23,48(tannin15),antibacillary of breath, myalgia, aches, nasal (p-cymene, acetic acid, alpha-phellan- congestion, sore throat, nausea, drene, beta-ionone, beta-sitosterol, vomiting, and diarrhea66-68. About 2- caryophyllene15) astringent16, 10% of COVID-19 infected patients hepatoprotective1,3,23,24,28 (tannin, p- have diarrhea, and the RNA of the cymene15), antihepatotoxic49 (tannin15), virus could be detected in stool and hypoglycaemic23 (inulin15), anti- blood samples69. Some cases are hyperglycemic(lupeol15), asymptomatic or lacking the typical hypolipidemic50(beta-sitosterol15), symptoms of fever, dry cough and, hypocholesterolemic(inulin, oleic acid, fatigue, and the diagnosis is based on stigmasterol, beta-sitosterol15), angiot- detection of the viral RNA in throat 7 SOHAG MEDICAL JOURNAL Saussurea costus may help in the treatment of COVID-19 Vol. 24 No. 3 July 2020 Mahmoud Saif-Al-Islam swab samples70. In the majority of ARDS, pulmonary edema, septic cases, the course of infection remains shock, and organ failure can occur66. mild71,72, and the patients resolve In some patients with SARS-CoV-2, spontaneously66. The patients can there is overexpression of inflam- develop bacterial and fungal infections matory mediators which is known as as the disease progresses. Therefore, cytokine storm syndrome (CSS) which antibiotic or antifungal treatment may also occurs in other inflammatory con- be given as appropriate73. Individuals ditions such as sepsis. It is unknown with multiple comorbid conditions are who will develop the cytokine storm. prone to severe infection67. CRP, serum ferritin, and IL-6 are early Fever can be treated with antipyretic biomarkers that may predict the drugs such as paracetamol, and patients evolution of CSS. These patients have with non-productive cough can be a much higher incidence of a rapid given expectorants such as guaife- deterioration of health and death81. The nesin74. Empirical early antibiotics cytokine storm is triggered by an were given for possible bacterial pneu- imbalanced response of type 1 and type monia75. 2 T helper cells67,82. Liver injury with various degrees Covid-19 patients had a thrombosis in may occur in patients with COVID-19 the small vessels of multiple organs. and the infection may be caused SARS-CoV-2 facilitates endotheliitis directly by the virus72,76. The incidence that may precipitate thrombosis83. of liver injury ranged from 14.8-53%, Respiratory failure in COVID-19 is not detected mainly by abnormal alanine caused by ARDS alone84, but micro- aminotransferase (ALT)/ aspartate vascular thrombosis may play a role as aminotransferase (AST) levels and well. This has important diagnostic and mild elevation of bilirubin levels67. therapeutic implications85. Whether the Gamma-glutamyl transferase and thrombotic process is directly caused alkaline phosphatase were elevated in by the virus or by the local or systemic 54% and 18% of cases77. The inflammation is not completely under- incidence of liver injury in severe stood86. COVID-19 patients was higher than Hypertensive, diabetic, older patients that in mild cases67,78 and signs of and those with coronary heart disease hepatic dysfunction may occur in were at higher risk of mortality71,72. critically ill patients72. One study Patients with myocardial injury are reported that serum ALT and AST older and have a higher prevalence of levels increased up to 7590 U/L and coronary artery disease, hypertension, 1445 U/L, respectively, in a severe heart failure, and diabetes mellitus than COVID-19