Spices are equally healthy as wild herbs in traditional medicine and can provide green medicine, as they are easy and fast to grow, considered safe to consume globally, contain bioactive ingredients such as polyphenols, and are highly antioxidant in nature [3]. So there is huge export scope too. Ayurveda also promotes synergistic mixture of ingredients and it is proposed here for the most potent spices. Fat medium such as Ghee (clarified butter) enhances the bioavailability of polyphenols such as Curcumin, a flavanoid [4]. Castor oil is another popular Ayurveda treatment for treat MSD. So the combination of fat and spice decoction will be tested in this project.

1. 1
OSTEOARTHRITIS- STUDY OF SPICE OIL MIX AS VEGETARIAN TREATMENT- CONCEPT
INTRODUCTION
Osteoarthritis (OA) is a leading (25% of the cases) musculoskeletal disorder (MSD) affecting that affect about 1.71
billion people in the world as per the World Health Organization (WHO) (https://www.who.int/news-room/fact-
sheets/detail/musculoskeletal-conditions). Knee replacement surgery is the a common treatment option promoted
today but is costly & has some negative health feedbacks. Lower back pain (LBP) is the leading MSD comprising
33% of the cases. Recent research has linked origin of OA & LBP and development on non-surgical treatments [1].
So, a common non invasive medical solution for both can benefit 60% of the MSD patients.
NSAID- non steroidal anti-inflammatory drugs such as Glucosamine and Chndritine are the standard health
supplements to treat osteoarthritis globally, despite their limited effect [2]. These have many adverse drug
reaction (ADR) such as stomach upset, ulcer or heartburn and may provide temporary relief, not the long term
solution. Hence, a long term solution is needed with improvement on American college ranking (ACR) criteria.
These are also animal products and the growing vegan or vegetarian population globally requires plant based
option and a crop to be viable.
Growing use & popularity of traditional medicinal systems (TSM) such as Ayurveda globally has threatened
hundred of rare medicinal plants o extinction. This includes the wild trees Guggul (Commiphora wightii) & Shalaki
(Frankincense, Boswellia serrata), whose gum is used in most potent Ayurvedic medicines to treat osteoarthritis.
But extinction threat has raised their prices & is causing adulteration & drug quality loss and loss of social faith in
TSM. They are slow to grow and yield gum after many years of gestation, so few farmers grow them. Hence,
seasonal crops can be viable option. Spices may be generally beneficial in MSDs but osteoarthritis needs study.
The number of vagan and vegetarian people in the world is growing and so is green spot mark on eatables
marketed. Medicines are not yet tagged as vegetarian or not, but some consumers may protest in future the use of
the standard drugs Glucosamine/ Chondritine animal origin, such as shellfish, causing a business risk.
Spices are equally healthy as wild herbs in traditional medicine and can provide green medicine, as they are easy
and fast to grow, considered safe to consume globally, contain bioactive ingredients such as polyphenols, and are
highly antioxidant in nature [3]. So there is huge export scope too. Ayurveda also promotes synergistic mixture of
ingredients and it is proposed here for the most potent spices. Fat medium such as Ghee (clarified butter)
enhances the bioavailability of polyphenols such as Curcumin, a flavanoid [4]. Castor oil is another popular
Ayurveda treatment for treat MSD. So the combination of fat and spice decoction will be tested in this project.
MSD have 3 common indications- inflammation, pain and wound. Hence, the proposed cure must address these 3
and the spices are selected are known to be effective so in earlier studies/ trials. The main active ingredient in the
spices selected show highly anti-inflammatory properties as studied by us recently to assess their molecular
docking scores that turned out to be very high (Black pepper- Piperine- 9.99 Kcal/ mol, Coriander- Apigenin- 8.63
kcal/ mol, Turmeric- Curcumin- 8.66 kcal/ mol & Ginger- 8 Shagaol- 7.51 kcal/ mol). This is similar to/ higher than
methotrexate (-8.6 kcl/ mol), the standard durg in rheumatoid arthritis, and also the spcially designed ‘best’
molecule- i4-(4-methyl-1-piperazinyl)-2-phenyl[1]benzofuro[3,2-d] pyrimidine [6] or isatin (benzohydrazide) [7].
Quercetin from Coriander, piperine has higher docking score (-12) than even the active ingredients of the
commonest herbal drugs Guggul & Shalaki (<10) [8]. 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 [8]. Ayurevdic drugs
are found to be effective in treating osteoarthritis [9] but this needs to be highlighted more.

2. 2
The proposed spices mix is found useful in osteoarthritis compared to napraxon, in a study in Iran [10]. We suggest
adding coriander to the mixture as it promotes pro-collagen forming [11] and is coolant vide Ayurveda, to balance
the hot properties the other 3 spices whose high consumption can have negative health effects such as blood in
the stools, pimples, rashes etc. castor oil trial was successful in pain reduction similar to diclofenac [12]. Earlier
studies in Pune in rat model also indicated utility of herbs, not tree gums, in recovery from osteoarthritis [13].
METHODOLOGY
A) In-vitro study- Synovial fluid culture- SFC culture from 30 osteoarthritis patients with prior informed
consent (PIC) and ethical guidelines will be tested with the proposed formulation- spice and oil mix.
Another group of 30 patients with standard health supplements Napraxone/ celecoxib will also be studied
and compared. One culture will be the control. Monitoring will be done after 7, 15, 22 and 30 days on the
basis of-
1- Rheumatoid Factor RF - significant concentrations in most people about 80
2- Complete blood count CBC - red and white blood cells and hemoglobin, calcium,
3- Comprehensive metabolic panel CMP - including uric acid to identify gout/ infections,
4- CRP test- C-reactive protein- increased level of CRP occurs in RA but not osteoarthritis. 5- Erythrocyte
sedimentation rate ESR - ESR is increased in RA but not in osteoarthritis.
6- Cytokines- ELISA- interlukins- IL-1, IL-6, IL-6, IL-15, IL- 17, Tumor necrosis factor- TNF- α, NKF-B, MMP- matrix
metallo-proteins (MMP), Immunoglobulin- IgG.
B) In-vivo study- Mice paw edema model in vivo - 10 mice 6- treatment, 4 standard / supplements.
Monitoring will be done after 7, 15, 22 and 30 days. One healthy mouse profile will be monitored similarly. The
parameters monitored will include a swelling & b IgG.
Pharmacokinetics study will be done (ADME- Absorption, distribution, metabolism and elimination), in silico-
preADMET, mice modeling will be performed.
C) Pre-clinical study- Above groups of 30 each osteoarthritis patients with spice mix and standard care
(Naproxen/ celecoxib).
RESULTS EXPECTED & OUTCOMES
The study will show if the proposed spice mix can relieve pain and inflammation and wound healing parameters.
Their dosage and processing method and format will be decided, if found useful in vivo & in vitro.
These spices are consumed widely globally & generally recognized as safe (GRAS) vide USA and Europe
pharmacopeia. So it can be exported when found successful. But their daily consumption may be below the
medical effect threshold required and this will be tested during the study.
Production costing, pricing, market potential and strategy will be indicated in the study and starup for that purpose
will be activated as required by BIG (Biotech Ignition grant) scheme of Dept. of Biotech. (DBT), Govt. of India.

3. 3
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