Open access peer-reviewed chapter

Polyphenols, Spices and Vegetarian Diet for Immunity and Anti-Inflammatory Drug Design

Written By

Utkarsh Ghate and Hema Kulkarni

Submitted: 22 November 2020 Reviewed: 10 April 2021 Published: 24 June 2021

DOI: 10.5772/intechopen.97661

From the Edited Volume

Bioactive Compounds

Edited by Leila Queiroz Zepka, Tatiele Casagrande do Nascimento and Eduardo Jacob-Lopes

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Much lower COVID-19 incidence and mortality in India compared to the Europe and northern America may relate to higher immunity possibly due to the low consumption of fast/packed food, liquour, tobacco, meat, HFSS- high fat, salt, sugar, besides higher exposure and a key blood protein. Indian spice intake is also double the world average and healthy cooking oil use such as Mustard, and may also explain it. Inflammation is the foundation for many ailments and challenges the immunity and vital in non-communicable ailments are at the centre stage in an aeing world. Polypehnols are crucial anti-inflammatory chemicals from spices that can for wellbeing and reduce adverse drug rections. We show this using Arthritis- a chronic auto-immune disorder, with the hlep of pharmacokinetic studies. Molecular Docking study was performed on the key bioactive compounds of important spices regarding COX2 active site (PDB ID 5IKR). Piperine in Black Pepper had most stability (Black Pepper, −9.99 Kcal/mol) followed by ‘Apigenin’ (Coriander, −9.63), and ‘Curcumin’ (Turmeric, −8.66) like quercetin in literature, and higher than the methotrexate (−8.6), the standard drug. Hence, their synergistic combination in fat medium such as clarified butter can lead the future drug design.


  • Polyphenols
  • immunity
  • health
  • spice
  • Corona
  • pharmacokinetic
  • inflammatory
  • arthritis

1. Introduction

Spices and herbs have been the key to the health security of the oriental world, besides in western world also until the last century. Polyphenols such as flavanoids are aromatic organic compounds having many health benefits being highly antioxidant in nature [1]. These are vital in preventing chronic or non communicable diseases (NCD) also called as “lifestyle ailments” that are common in the western world [2] and the elderly (over 60 years of age), whose share in the world population is growing rapidly, from 10 to 20% of the total [3].

Inflammation and immunity are most important concepts in medicine today, as cause and remedy respectively [4]. Inflammation is the chief mediator behind chronic or lifestyle ailments prevalent today such as heart disease, cancer, diabetes and blood pressure triggering vigorous research on anti-inflammatory and/or immunity booster phytochemicals, for safety and efficacy (ibid.).

Antioxidants are able to reduce oxidative damage to the tissues and protect or restore immunity & health. Vegetarian diet especially fruits, vegetables, pulses are rich in antioxidants, including polyphenols. Spices are among the richest in these, and are anti-inflammatory. Thus, they can be useful to manage immunity disorders such as COVID-19 and Arthritis, an auto-immune disorder of the elderly.

Adverse drug reaction (ADR) is another major concern that spice/herbal medicines can reduce in principle and as experienced, leading to their growing global demand. ADR affects about 5–10% of the patients globally and can cause sever damage/expenses [5]. As spices are permitted food ingredients globally, ADR risk is low.


2. Covid-19 and vegetarian, spice diet relation

The COVID-19 burden cross top 10 infected countries (dt. 28 Feb. 2021) is shown in the Table 1 and India is the 2nd most infected after USA but its no. of cases (incidence) and per million (7,990) and deaths (113) is the lowest. It is only 16% of the average (47,000/ 1 million) of the other 9 leading countries incidence and 10% of the death rate (1,110/1 million). This makes it worth studying.

2.1 Immunity Buster foods

It is known that the Immunity is compromised by the higher consumption fast/packed foods, refined cards, intoxicants, higher salt, sugar, fat etc. We find the immunity stress foods consumed in 2–30 times in EU/USA (average 9 times intake) than India, as seen in Tables 2 and 3, Figure 1.

CountryTotal CasesTotal DeathsTot Cases/1 M popDeaths/1 M pop
1. USA29,202,966524,67087,8861,579
2. India11,097,134157,0927,990113
3. Brazil10,517,232254,26349,2481,191
4. Russia4,246,07986,12229,088590
5. UK4,170,519122,70561,2221,801
6. France3,736,01686,33257,1531,321
7. Spain3,188,55369,14268,1801,478
8. Italy2,907,82597,50748,1401,614
9. Turkey2,693,16428,50331,708336
10. Germany2,444,30370,60829,112841

Table 1.

COVID-19 Incidence and death rate in top 10 countries.

1. AlcoholLit/ yr5102
2. Cigarettesno.s11714009
3. SugarKg/yr19352
5. MeatKg/yr58817
6. FatsGram/day451453
7. SaltGram/day10343
8. Refined carbohydrates kgKg/yr.1.55030
9. Packed foods%<54510

Table 2.

Immunity Buster Foods Intake Globe per capita/yr. [2].

ItemDeveloping% ShareIndustrial% share
veg. Oil2391149418

Table 3.

Various food items share in Calorie intake (Kcal/day/head) [6].

Figure 1.

Food items % in Calorie intake- nations.

2.2 Immunity booster foods

Indian spice consumption, rich in polyphenols, is 2 times higher (2.07 kg/head/year, Table 4 and Figure 2) than the global average (1.01 kg/head/year) [7] or USA [8]. Cancer incidence (89 per 0.1 million) in India is 50% of the global average (197) 25% of the EU (363) or USA (387), indicating better immunity [9], possibly due to the higher spice consumption. Asthama incidence, a major respiratory ailment and immunity indicator is similarly low in India with below 10% population affected but higher levels in the European nations- 20 to 25% [10].

Parameter- regionIndia [7]USA [8]Ratio Rest/India
Spice intake kg/head/year10.60.6
Cancer prevalence [9]893634

Table 4.

Spice Intake & Cancer incidence- India & the world.

Figure 2.

Spice intake & Cancer Incidence (Note- the Y axis is in the log scale so the world and India incidence is less distinct).

However, the spice consumption in India varies greatly across states and economic strata or ethnicity and has changed over times much. Chilli for instance, has replaced black paper, common earlier for adding pungent flavor and changed the world history as European discovered India for the later. The former has no antiviral report [11] while the later is an effective antiviral [12]. Similarly, Chilli is consumed more in northern India while Black Pepper in southern India- its main producer region- and this region also shows lowest fatality rate in India- 1%. Chilli comprises nearly 20% of the 5 gram/day/head spices consumed, and Turmeric, Ginger, Mustard, Coriander, Cumin are nearly equal, the 5 adding to 80% of the spices consumed on average [7]. More potent antiviral spices (except Ginger & Turmeric) are consumed to lesser extent viz. Cinnamon, Clove and Garlic. The potential of spice bioactive agents as possible COVID-19 remedy or relief is enlisted in Table 5.

1. CorianderQuercetinAttachment, endocytosis, cell fusion [13, 14]
2. GingerGingerolSecrete IFN-β t, inhibits initiation of virus - reduces HRSV-induced plaque [15, 16]
3. TurmericCurcuminAnti-inflammatory, used in rhinitis [17]
4. Pepper, BlackPiperineAnti-proliferative activity- in vascular smooth muscle cells [18]
1. CamphorImine1,7,7-trimethylbicyclo [2.2.1] heptanes2-ylidene [19]
2. CuminEHP [1-(2-Ethyl,6-Heptyl) Phenol]Vero cell membrane and/ or HSV-1 envelope [20]
3. CloveEssential oil, EugenolEnveloped virus- HSV-1 and Newcastle [21]
4. Garlic, OnionAllicinBlock multiplication [22]
5. Tulsi (Holy Basil)Terpenoid, polyphenolsNon- neuraminidase inhibition [23, 24]

Table 5.

Spices with scope of COVID-19 immunity/cure.

Scientists have postulated other hypotheses to explain the much lower COVID-19 prevalence and mortality in India/Asia than in the Europe & America, such as the hygiene/exposure [25] and genetics [26], but the role of diet is also mentioned in both prevention and treatment with immunity focus [27]. Spices are found to be important preventive agents and immunity guards in case of the corona, based on data from 163 countries by German scientists [28].

Spices can be important immunity booster due to their bioactive compounds known to be healthy [29, 30]. They may be suppressing the inflammatory pathways NF-κB and STAT3 [31]. Flavonoids inhibit biosynthesis of prostaglandins (the end products of the COX and lipoxygenase pathways), which acts as a secondary messengers and are involved in various immunologic responses [32]. We illustrate below the scope of use of bioactives from spices to treat Arthritis, a common auto-immune disease with no sure modern cure yet, as drug design example to integrate the traditional wisdom with modern science and technology. But we present some other correlates of Corona intensity and mortality before that in Table 6.

StatePopu-lation MillionPopu-lation Density@Corona cases nos.Corona – Deaths Nos.Corona Cases/millionCorona Fatality %**Income*Literacy#
Tamil Nadu7255587321912641121281.455487
West Bengal9110295838391032264161.773576
Ttar Pradesh199828610273878330671.442067
Correlation coefficient0.38−0.070.710.76
Correlation betweenCases-Populn. DensityFatality-Case densityCase density- IncomeCase density- literacy

Table 6.

Corona intensity & socio-economic correlates across Indian states.

no. k/ sq. km.

70% of India.

80% of India.

2011 census data.

Rs. K/head/yr- ref. RBI, 2020.

(deaths/ cases), M.P.- Madhya Pradesh Ref.-, Dt. 28-03-2021.

Table 6 shows that the corona intensity (no. of cases/ million) is strongly (r = 0.7) correlated with the income per capita and even strongly (r = 0.75) with literacy. The lower corona burden in India and its poorer states may also be because the poorer, illiterate people of states such as U. P., Bihar have stronger immunity, despite higher population density. For, they mainly eat natural foods, with very low amount of packed food, bottled water so low HFSS intake. Hence, the lesser Covid-19 intensity in North & eastern India. Corona is mainly rich countries & people’s ailment [33]. Lac of hygiene & exposure to microbes in the slums etc. makes people resistant to microbes, it is said [34]. Migrations improve immunity, is another hypothesis [35]. Mustard oil, common in northern India is antiviral & SARS inhibitor [36], unlike Groundnut in western India, which is an allergen. Lastly, Asians got a protein D614 mutation, making them stronger than the Europeans [37]. These 5 reasons may explain the trend besides Govt. advisory on spice decoction (“Kadha” in Hindi-

Its rationale and working mechanism is also explained by scientists [38].

2.3 Spices and herbs- global resurgence

Scientists from Russia & USA describe the health benefits of spices due to their bioactive ingredients & antioxidant nature [39]. They say rosamarinic acid content from the Mint family as beneficial (Oregano- 2,562 mg/100 gm dry weight, Sage- 2,186, Mint- 1908, Sweet Basil- 1,086, & Thyme- 681). Aromatic and medicinal herbs or spices such as these and Parsley, Coriander, Onion, Cumin, Cinnamon, Bay etc. (except Chilli) protect human health due to flavanoid content e.g. Quercetin, Luteolin, Rutin, Apigenin, Myicetin. They indicate that the the herbs are found useful in treating the cancers below-

  1. Turmeric- Rectal, oral, head, neck, Leukemia;

  2. Saffron- Skin, rectal, hepatic,

  3. Garlic- prostate, colon,

  4. Onion- Gastric,

  5. Mustard- Rectal, Bladder,

  6. Bayleaf- melanoma.

They also mention the spices as having therapeutic effects below

  1. Cardiovascular- garlic, Turmeric, Ginger

  2. Neuro-degenrative- Mint, Onion

  3. Antidiabetic- Cinnamon, Bayleaf, Fenugreek, Mustard

  4. Gastrointestinal- Black Pepper, Bayleaf

  5. Hypertension- Cardamom, Cinnamom,

  6. Hepatic- Caraway, cardamom,

  7. Endocrine- Ginger, Turmeric,

  8. Obesity- Saffron, Turmeric,

  9. Renal- garlic, Fennel, Ginger,

  10. Alcohol abuse- Thyme, Ginger

Due to the efficacy, safety and sentiments, herbal medicines top the complimentary & alternative medicine (CAM) treatements becoming popular globally recently. The amount of money spent on CAM treatments in the U.S. has skyrocketed in recent years. As per an 2007 survey, Americans spent $33.9 billion out of pocket on CAM therapies that year [40]. About $22 billion was spent on natural products, instructional classes, and materials. Dietary supplements accounted for $14.8 billion of this amount, an expenditure equal to about 1/3rd of out-of-pocket spending or prescription drugs. The remaining $11.9 billion was spent on an estimated 354 million visits to CAM practitioners (acupuncturists, massage therapists, or chiropractors), an amount equal to about 25% of out-of-pocket costs for visits to conventional doctors. The following 10 species (3 spices, 4 herbs) prevail [40]

  1. Echinacea- 41%,

  2. Ginseng- 24%,

  3. Gingko biloba- 21%,

  4. Garlic - 10%,

  5. St. Johnʼs wort- 12%,

  6. Glucosamine- 12%,

  7. Peppermint- 12%,

  8. Fish oil/omega-3-10%,

  9. Ginger - 10%,

  10. Soy - 9%.

The main ailments by frequency referred to the CAM practitioners are

  1. Back pain- 17%,

  2. Neck pain- 6%,

  3. Joint pain- 5%,

  4. Arthritis- 3.5%,

  5. Anxiety- 2.8%,

  6. Cholesterol- 2.1%,

  7. Head or chest cold- 2%,

  8. Other musculoskeletal- 1.8%,

  9. Severe headache or migraine- 1.6%,

  10. Insomnia- 1.4%.

Reasons for the Increased Use of CAM and Dietary Supplements are

  1. the increased availability of information on the Internet

  2. increased contact with other cultures that traditionally use CAM.

  3. Renewing d interest in formerly countercultural ideologies, such as environmentalism.

  4. the perception that CAM is easier to understand, safer, and less expensive than conventional medications.

  5. distrust of and frustration with the health care system.

  6. a growing recognition that many factors contribute to health and well-being.

With the growing use of the herbal medicines, safety concern is emerging due to the issues such as adulteration, quality and adverse reaction [41]. Hence, World Health Organization (WHO), devised a Traditional Medicine New Strategy (2006–2013) with 3 key health priorities [42], as most countries have traditional/herbal medicine policy to mainstream it

  1. mental health,

  2. non-communicable diseases and

  3. universal health coverage.

Nevertheless, spices and herbs have great potential in future as depicted below with in the example of an anti-inflammatory drug design excercise.


3. Arthritis drug design

There are globally 1.3 billion cases of musculoskeletal disorders and over 121,000 deaths from such disorders, as well as nearly 139 million disability-adjusted life years, or the number of years lost due to ill-health, disability or early death [43]. Globally, the proportion cases in are led by the low back pain (37%); followed by “other” (21%); osteoarthritis (19%); neck pain (18.4%); gout (2.6%); and rheumatoid arthritis (1.3%). These proportions changed little from 1990. Surgery and the NSAID- Non steroidal anti-inflammatory drugs- are costly and cause adverse effects such as gastric and cardiovascular issues. The herbal medicines are perhaps effective and in growing demand and even exported much, as dietary supplements that are common globally and many having positive outcomes at least in the short term [44, 45]. But herbs they use are and are often adulterated such as Shalaki (Indian Frankincense/Olibanum, Boswellia serrata) or Guggulu (Indian Myrrh, Commiphora wightii, [46]. Hence, sustainable ingredients from farm are needed such as Drumstick (Moringa olifera tree leaves), rich in calcium and highly exported [47]. Glusosamine, a popular health supplement in arthritis is a sea shell product [48]. So it needs a vegetarian option due to the growing trend of veganism globally. Spices can address this as they contain the bio- actives to relive Arthritic pain and inflammation- Vitamin A, C & K, polypohenols, Omega 3 fatty acids, and minerals Calcium, Magnesium, Iron and Zinc [29].

Even in India, about 40% the elderly may be Arthritis affected, it is said in the study by All Indian Institute of Medical Science in metros such as Delhi AIMS [49].

Bioactive ingredient levels are low in the general market samples of spices such as Black pepper (Piperine- 2-4%), Coriander (Quercetin- 0.12%), Turmeric (Curcumin- 2-3%), as the critical agri-inputs to increase the polyphenol content e.g. Potassium for Curcumin by 50% in Turmeric [50, 51]. Higher Potassium inputs also enhances oil content in Coriander [52], for instance. So improving agro-technology can enhance the bioactive potential of the spices.

We demonstrate here the comparative advantage of spices over the standards drug for the treatment of arthritis, to illustrate the alternative approach to drug discovery. Hence, we performed docking study at Rasa Life. Co., ( Pune during 2020 on the key bioactive compounds important spices w.r.t. COX2 (cyclooxygenase) active site (PDB ID 5IKR obtained from PDBsum). Table 7 shows that the 4 spice ingredients have closeby values and high theraupetic potential are viz. Piperine (Black Pepper, −9.99 Kcal/ mol) ‘Apigenin’ (Coriander, −9.63) and ‘Curcumin’ (Turmeric, −8.66 with the stability than methotrexate (−8.6), the standard NSAID [53]. The values are also higher than the synthetically designed ‘best’ molecule- i.e. 4-(4-methyl-1-piperazinyl)-2-phenyl[1]benzofuro[3,2-d] pyrimidine discovered in the Saudi Arabia [53] or isatin (benzohydrazide) [54]. Ginger (−7.51 kcal/mol- 8-Shagaol), and Diosgenin from Fenugreek had the lower than the threshold values (−6.8) so are not considred here here. Other traditional medicine such as Ayurvedic top used herbs such as Behera (Terminalia bellerica) & Herra (T. chebula) have also shon high anti-inflammatory potential against COX-2 [55].

SpiceIngredient (conformation)Site & activity (interactions)- (PDB id 5f19)Binding energy (kcal/mol)Remarks
High potential
PepperPiperine (53)SER530 & ARG 120 (2)−9.99Good activity, high probability
CorianderApigenin (20)QuercetinTRP 387 & ASN 382 (2)ALA199, TRP 387 and ASN 382, TRP387, TYR385(A)−9.94Stable, high probability
TurmericCurcumin (35)TYR 385- good activity (1)−8.66-“-
Less scope
Ginger8-shogaol (40)Amino acid residues- SER530 & MET522 (2)−7.51Stable, good activity, high probability
10- Gingerol (40)TYR385- Good activity (1)−7.34-“-
FenugreekDiosgenin (20)HIS214 (outside site)−6.80outside, not feasible
CloveEugenolSER 530 & TYR 385(Chain A)−6.33Stable, high probability

Table 7.

Docking study results of Spices active ingredients in COX-2.

The earlier tests of herbal ayurvedic medicines in Arthritis treatment yielded encouraging results in Pune city [56], India, and in USA [57]. So this approach needs further exploration. Quercetin from Coriander & Onion, peppers has higher docking score (−12) than even the active ingredients of the commonest herbal drugs Guggul & Shalaki (<10) [58]. Quercetin is also found to be more effective than even aspirin or celecoxib in the inflammation markers cyclooxygenase (COX) that are vital in cancer biology vide studies in Russia [59] and also in India [60]. Hence, the use of these novel molecules in the arthritis context may be found safe, effective and sustainable.


4. Conclusion

Immunity decline is a major cause of the pandemics in the last century and thus inflammation control is a major challenge for healthcare system. Spices and herbs, rich in polyphenols can be vital tool in this regards as they have high antioxidant value and reduce the oxidative damage to the body. Much greater share of vegetarian diet and spices, besides less intensity of packed foods, meat, liquor, Tobacco, refined carbs, soft drinks etc. in India may be driving its higher immunity and lower burden of COVID-19. Pharmacokinetic methods such as molecular docking can be used to design drugs for immunity building and inflammation control. This is shown with the example of Arthritis where Black Pepper, Coriander & Turmeric can provide potent drugs vide docking studies with focus on piperin, quercetin/ apigenin & curcumin.


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Written By

Utkarsh Ghate and Hema Kulkarni

Submitted: 22 November 2020 Reviewed: 10 April 2021 Published: 24 June 2021