Rakhi Mishra,Binit DwivediDr.D.P.Rastogi Central Research Institute for Homoeopathy,Under Central Council for Research in Homoeopathy,Ministry of AYUSH,Government of India.

Abstract Camphor(C10H16O)is a white crystalline solid exist in enantiomeric form R and S camphor.It is a terpenoid obtained from turpentine oil.Synthetically it is synthesized by catalytic process as alpha pinene.Naturally camphor is obtained by steam distillation of woods of Cinnamomum camphora tree,also known as Camphor tree,camphor laure and camphor wood.Camphor has many pharmacological properties.It acts as antiviral,anticancerous,antimicrobial,insecticidal,anticoccidial,anti-nociceptive and antitussive drug.In addition,it can be used as skin penetrating enhancer.Camphor gives a soothing and cooling effect,which helps to reduce pain.The reason behind its soothing effect is camphor act as a counter-irritant by activating heat sensitive transient receptor potential vanilloid subtype 1 and transient receptor potential vanilloid subtype 3 receptors and inhibits the transient receptor potential melastatin-subfamily member 8 receptor.As a result,these receptors provide a sensation of scalding heat and pain(nociception)and could be used to treat neuropathic pain associated with multiple sclerosis,chemotherapy,or amputation,as well as pain associated with the inflammatory response of damaged tissue such as in osteoarthritis.Camphor has a history of epidemics cure.During leishmaniosis(kala-azar)pandemic in 14th century,camphor was used as fumigant to control the spread of plague in European countries.In 19th century when cholera,small pox and influenza spreads,camphor was used as mothballs in Indian subcontinent as a(cough reliever)agent.During 18th century Russian influenza “flu pandemic” founder of Homeopathy Hahnemann in 1831,published his research work on camphor and suggested camphor as a“divine remedy”for influenza given in extremely small doses.In the same year,several companies launched to sell menthol rub as natural rub ointment consisting camphor as prevention measures for spread of influenza.As the recent epidemic of COVID-19 arises,prevention and control of spread of disease is an alarming issue.This article covered the glimpse of uses and importance of camphor in the history of epidemic cure.

Key words:COVID-19,Cinnamomum camphora,Camphor,Epidemic

Background

Corona Virus Disease 2019(COVID-19)is an infectious disease caused by SARS-CoV-2.There is no specific treatment available for COVID-19;Prevention and control of the spread is an alarming issue[1].According to the World Health Organization the global number of new cases was increasing day by day[2].In this situation,repurposed antiviral and immune modulating drugs are used compassionately.Camphor was used as fumigant during the Black Death break out,and also was considered as a valuable source of antiviral drugs.Historically Marco Polo in the 13th century and Camoens in 1571 mentioned camphor and called it as “balsam of disease”.Camphor was one of the therapeutic agents of the 19thcentury pharmacopeia used as an analgesic[3],expectorant,counterirritant and abortifacient,as well as stimulant.Inhaling camphor increases blood oxygen level in the body,few drops of camphor oil can help improve oxygen levels.This helps increase oxygen levels and congestion.In 19thcentury,the founder of homeopathy Samuel Hahnemann suggested camphor as divine remedy for the cure of diseases given in extremely low doses.He later writes camphor is the great cholera prophylactic and alone can cure epidemic.Recently during COVID-19 break out,Homeopathy guidelines was issued by Ministry of Ayush,government of India for public notice for Genus epidemics identified by the designated experts for immunity enhancement and practitioners may suggest the same to the people.In this guideline,as a Homoeopathic remedy Camphora was suggested for symptomatic amelioration of mild disease[4].Camphor is FDA approved topical antitussive,analgesic,anaesthetic drug used to treat cough,relieve pain and skin itching problems.Camphor has many pharmacological properties;it acts as insecticidal,antimicrobial,anticancerous,antiviral,anticoccidial,anti-nociceptive,antitussive drug[5].So,camphor can be used as antiviral drug for COVID-19 pandemic.Cinnamomum camphora(C10H16O)is a terpenoid with white crystalline solid[6]in appearance and having aromatic odour[7].It is a terpenoid exist R and S camphor(Figure 1).

Figure 2 Wagner Meerwein rearrangement of camphene to camphor

Extracted from turpentine oil,it is synthesized as alpha pinene[8].In catalytic process acetic acid solvent undergo catalysis reaction with strong acid and the product formed is camphene.Camphene undergo Wagner Meerwein rearrangement and form isobornyl cation captured by acetate.Formed Isobornyl acetate further undergo hydrolysis and form isoborneol.This Isoborneol undergo dehydrogenenation and form camphor as product[9](Figure 2).In synthetic process racemic mixture of camphor formed in equal ratio of(+)and(–)camphor.

While natural camphor is obtained by steam distillation of the wood fromCinnamomum camphoratree.The camphor tree is easily found in Asian countries.Cinnamomum camphoratree also known as Camphor tree,camphor laure and camphor wood.The history behind the camphora species name is more adventurous as it comes from the Malay Proto-Austeronesian language,from the word“qapuR”,which means lime and calcium.Then in Sanskrit language it is pronounced as“karpūraḥ”then it reaches to Arabic and Medieval Latin to French as “camphre”.Camphre in the Neo Latin form of “camphora” gave the name to the species[10–13].

Camphor exerts an analgesic action by producing warm sensation,observed by exciting desensitize heat sensory nerved by activating heat sensitive transient receptor potential vanilloid subtype 1(TRPV1)and transient receptor potential vanilloid subtype 3(TRPV3)receptors[14](Figure 3)[15].Additionally,camphor was shown to inhibit the transient receptor potential melastatin-subfamily member 8(TRPM8)receptor response to menthol.TRPV1 receptors are non-selective cation channels that are sensitized from noxious stimuli,leading to inflammatory conditions and pain.In chronic pain states,vanilloid(TRPV1)receptors[16]are upregulated on neurons,have reduced stimulation thresholds,and cause an increased perception of pain.The function of TRPV1 is detection and regulation of body temperature.In addition,TRPV1 provides a sensation of scalding heat and pain(nociception).TRPV1 receptors could be used to treat neuropathic pain associated with multiple sclerosis,chemotheraphy,or amputation,as well as pain associated with the inflammatory response of damaged tissue such as “osteoarthritis”.In primary afferent sensory neurons,it cooperates with transient receptor potential cation channel subfamily A member 1(TRPA1)to mediate the detection of noxious environmental stimuli.

Similarly,TRPV3 transient receptor potential cation channel,subfamily V,member 3,also known as TRPV3,is a human gene encoding protein of the same name.The TRPV3 protein belongs to a family of nonselective cation channels that function in a variety of processes,including temperature sensation and vasoregulation.The thermosensitive members of this family are expressed in subsets of human sensory neurons that terminate in the skin,and are activated at distinct physiological temperatures.This channel is activated at temperature between 22˚C and 40˚C.The gene lies in close proximity to another family member(TRPV1)gene on chromosome 17,and the two encoded proteins are thought to associate with each other to form heteromeric channels.This is the reason why camphor act as a counter-irritant as it first produces a feeling of warmth by increasing the blood flow.Later on,it gives a soothing and cooling effect due to its cold nature,which helps to reduce pain when camphor is applied on the affected areas.

Camphor has many pharmacological properties such as insecticidal,antimicrobial,anticancerous,antiviral,anticoccidial,antinociceptive,antitussive activities.In addition,it was used as skin penetrating enhancer.The antiviral property of camphor has been exploited for controlling COVID-19[17].This article covered the glimpse of uses and importance of camphor in the history of epidemic cure.

Chemical constituents of camphor

Menthol,thymol,salicylic acid,phenol,napthol are the fragmentedcompoundsobtainedfromtheCinnamomum camphora.Campher,campherol,cineol,camphene,dipentene,terpineol,candinene,safrole,camphorace,laurolitsine,reticuline are the main active constituents ofCinnamomum camphora.The reason behind the strong fragrance of its barks is the presence cinnamaldehyde compound.The leaf contains eugenol and isoegnol for which its leaf imparts hard odour.It also contains the active minerals camphor,which is responsible for its overall properties.Cinnamomum camphorawhole plant contains a volatile oil,camphor,safrole,linalool,eugenol,terpenol and lignans(including secoisososolariciresinol dimethyl ether and kusunokiol).The presence of safrole in the plant has carcinogenic property.The leaf oil is a natural resource of linalool(94.9%)and citronellal(2.4%)[18].

Properties of camphor

Camphor is FDA approved topical antitussive,analgesic,anaesthetic drug used to treat cough,relieve pain and skin itching problems.Camphor is readily absorbed through the skin and produces either a coolness or warmth sensation and act as local anaesthetic and antimicrobial agent[19,20].It is used mainly in skin disorders problems.It relieves pain in muscle cramps,when mixed with effective oil base for example mustard oil.Very effective for treatment of acne,acne scars,when mixed with coconut and olive oil.Great chest decongestant and can be used in vapour form for cough and cold.It is used as cough suppressant and as a decongestant[21]and used as active ingredient as a vapour steam products in Vicks vapoRub.It can be used as an effective treatment for hair loss,applied when mixed with coconut oil or mustard oil.It can cure hair related problems such as dandruff,head lice and itchy scalp.It is a great stimulant for the heart and the whole circulatory system.It can be used as a mouth cleanser to cleanse the saliva and improve the sense of taste.It also helps in improving the digestive secretions when consumed in small quantity.It act as great diuretic and keeps the urinary system free of bacterial infestation.Camphor has analgesic action,when applied topically it produces a warm sensation.It activates heat-sensitive transient receptor potential vanilliod subtype 1(TRPV1)and(TRPV3)receptors which excites by activating desensitizes sensory nerves[22].Camphor as an essential oil has properties of an antispasmodic stimulant,anti-neuralgic,decongestant,sedative,anti-inflammatory,anaesthetic,antiseptic and nervous pacifier,and disinfectant and insecticide substance.Camphor was also used in ancient Sumatra,Indonesia to treat sprains,swellings and inflammation.During 14thcentury plague the Black Death,outbreaks of small pox and cholera,Camphor was used as fumigant and considered as a valuable source of antiviral drugs[23].Since COVID-19 is also an infectious disease caused by the “novel corona virus”.Common symptoms are fever,dry cough,breathing difficulty.Some patients also have aches and pains,nasal congestion,runny nose,sore throat,nausea,vomiting or diarrhoea problems.As per the Advisory issued by Ministry of AYUSH.As a therapeutic aid camphor has been suggested and patients of COVID-19 are to be treated with adjuvant Homoeopathic medicines with the permission from local health authorities and Medical Superintendent of the Hospitals and Homoeopathic doctors in India.In 18th century,camphor was used by Auenbrugger to treat mania.In the cholera epidemics,Naples(1854-1855)the alcoholic extract of camphor was used to treat cholera[24].In 1990s,camphor used to administer orally in minor quantity for minor heart symptoms and fatigue[25].It was sold under the trade name Musterole,production ceased in the 1990s.

Anti-oxidant effects

Camphor act as strong Anti-oxidant agent[26]that kills away the free radicals in your body,thus preventing many liver disease and tissue ruptures and hurt troubles[27].It suppresses the effect of oxidative stress and act as strong antioxidant agent.The main mechanism of action of camphor is camphor act a rubefacient when it is rubbed on the skin and causes localized vasodilation,which gives feeling of comfort and warmth[28].When camphor applied gently on the skin,it acts as antipruritic agent and creates coolness feeling and a mild local anaesthtic effect and relieves itching.When ingested in small amounts,it creates feeling of warmth.Camphor acts as local anaesthetic on the respiratory passageways and causing cough suppression[29].

Antispasmodic effects

The monoterpenes present in the camphor showed Antispasmodic activity[30].It provides instant relief from spasms,cramps and provides relief to stomach.Camphor is commonly applied as a topical medication as a skin cream to relieve from joint pain[31].It easily absorbed in the skin epidermis[32]where it stimulates nerve ending sensitive to heat cold and produces a warm and cool sensation to the body.

Anti-inflammatory effects

It helps to decrease the cholesterol level in the body also helpful in relieving muscular pain,aches,chest congestion as well as rheumatism.Camphor oil has anti-inflammatory properties and is often used as an ingredient in vapour rubs,liniments and balms[33].

Act as Fungicide

Camphor helps to cure fungal infection that occurs on nails and skin.Camphor is the essential bioactive compound ofCinnamonum camphoraoil,exhibit strong antimicrobial activity by inhibiting pathogenic microorganisms including fungi[34].

Antiarthiritic effects

Camphor is known agonist of transient receptor potential vanilloid subtype 2,TRPA1 as well as TRPV1 quickly deactivating transient receptor potential channels resulting in long-term pain relief[35].It helps to cure swelling of various body parts,which give relief to joints pain and help to improve the condition of pain related problems.It is a common ingredient in pain relief medications.It may help to treat muscle aches and pain while stimulating circulation by interacting with receptors on the sensory nerves.Camphor induced blockade of TRPA1 as well as desensitization of TRPV1,underlies the pain relieving effects of camphor[36,37].

Narcotic effects

It helps to relax the brain and nerves and act as narcotic[38].It has been applied as a topical anti-infective and anti-pruritic and internally as a stimulant and carminative[39].

Indications and Usage of Camphor

Camphor uses are different in different countries.It is used in the form of medicine,food-flavouring agent,in religious function,in aromatherapy and as a pain-relieving agent.Chinese uses camphor as a circulatory stimulant and healing agent whereas Japanese uses it as torch light material and add it in small quantity into fireworks to brighten the light.In India camphor relates to spirituality and used in temple during morning and evening rituals.In household,it is used as camphoric fumes to clean the environment of house.Scientifically it is non-irritant to eyes[40]and used in many religious functions in India.In modern allopathic medicine,medicines containing camphor is used to relieve pain caused by breast engorgement by intramuscular injections[41].

Cough

Cough is caused by poor digestion.Poor diet and fails to eliminate waste from the body leads formation of toxicity in the body in the form of mucus in the lungs.Edible camphor has a good role in reducing improper digestion and helps in expelling the mucus from the lungs because of its cold property camphor is beneficial in managing cough and its associated symptoms.Camphor possess antitussive activity.Camphor is a rare herb which being coolant,balances Kapha Dosha and reduces fat and cholesterol levels.Camphor is also used an aerosol by steam inhibition,inhibit coughing and relieve from congestion due to common cold[42].

Pain reliever

It is very good pain reliever,and very effective in convulsions and respiratory disorders.It has good role in respiratory system as it helps in expelling extra amount of mucus in the respiratory tract and improves the condition of throat and helps in increase in urine output.When given in calculated amount it works as aphrodisiac agent.It also acts as antipyretic agent and hence decreases the aggravated body temperature[43].

In respiratory disease

Camphor,if taken internally in small doses acts as carminative,reflex expectorant and reflex stimulant of heart circulation as well as respiration.In convulsions,hysteria,epilepsy and chorea it is used a sedative and nervous depressant.It is used as rubefacient and mild analgesic topically.Camphor is used externally in catarrhal diseases of the respiratory tract and muscular rheumatism and internally in hypotonic circulatory regulation disorders.

Indigestion

One of the reasons f or indigestion is weak digestive fire;edible camphor helps to improve the weak digestive fire because of its appetizer and digestive properties.However,it is advisable to consume camphor in small amount.

Obesity

Diet and lifestyle are one of the major reasons behind increase in obesity.This weakens the digestive fire increases accumulation of toxic chemicals,and leads to fatty tissues imbalance and weight gain.Edible camphor improves the digestive secretions and reduces toxicity in the body because of its appetizer and digestive properties.Edible camphor has also scrapping property as it helps to remove all the excess fat from the body[44].

Pneumonia

It can improve chest congestion and inability.It is also used in high-grade fever,headache,delusions,and paralysis case[45].

For skin treatment

Camphor has anti-fungal properties and has very good effect in skin infection.Camphor has been applied to relieve skin pain and reduce itching.Camphor stimulates the nerve endings that relieve pain and itching.It can be used in case of fungal infection,as camphor is active against the fungi.While before using camphor directly caution has to be taken to broken skin,as it enter the body quickly[46].

In homeopathy

In homeopathy,camphor is known as “Camphora”which is derived from the compound camphor.Founder of homeopathy Samuel Hahneman suggested the use of tincture and named it as “divine remedy”.He further suggested that camphor could remove pathological effects of many other drugs including homeopathy remedies.Camphor can be antidote opium.The prescribed dose is usually given in the form of(camphor 1M).In homeopathy camphor 1M given in the cases of congestion,cough suppressant,sneezing,coldness,in case of collapse due to feverish condition.It is taken as strictly taken care of under medical supervision as it acts as an antidote to most of the homeopathic remedies[47].It is highly effective in treatment of weakness of body and provides relief in cold.Also used as heart health tonic,increase blood flow &improved the function of hearts.Useful for people suffering from headache with fever,body pains and helps in relief of blocked nose

The epidemic control history of Camphor

14th century Black Death

During the Black Death epidemic of 14thcentury,camphor was used as fumigant to control the spread of plague in European countries.Similarly,during the outbreaks of small pox and cholera,Camphor was considered as a valuable source of antiviral drugs[48,49].During the era of the Black Death rosewater together with camphor as a perfume ingredient was sprinkled over corpses before shrouding.It was topically applied as analgesics and rubefacients for the treatment of muscle aches and pain.It was mentioned in scientific result,that camphor act as antitussive,stimulate “the cold receptors” in the nose,which helps in relief during cough[50,51].When camphor vapours were administered,it significantly reduces the chances of cough frequency almost thirty percent of total frequency[52].

19th century influenza

Later in 19thcentury epidemics when cholera,small pox and influenza spread,camphor shows its significance cure for epidemics.During 19thcentury epidemics,camphor used as mothballs in Indian subcontinent to kill insects and germs because of its properties to act as antimicrobial,antiviral and antitussive(cough reliever)agent[50].Camphor activates cold receptors identified as TRPM8,the minty–cool ion channel whereby TRPM8 activations increased cough latency whilst reducing cough frequency and give relief in cough.During that time people used variety of measures to try and protect themselves from the flue.People might wear a bag of camphor around their neck to ward off the virus,while nurses and doctors inject it into an infected patient’s arms and legs with a hypodermic needle[53].

18th century Russian influenza

In 18thcentury,Russian influenza came as flu.The epidemic originates in Russia and spreads over whole Europe.At that time,Hahnemann suggested prompted cure for smelling camphor solution from which person got relief in 24 hours.Camphor proves to be great success in curing cholera prophylactic and alone can cure the epidemic.Camphor has the capacity to destroy smallest animal of the lower order very quickly and is therefore capable of destroying and eliminating the cholera disease,which consists of imperceptible living organisms fatal to human,which attach itself to skin,hair,or clothing and is thus transmitted unnoticed from one person to another.Hahnemann noticed that at early stage prevention from cholera camphor is very effective.Later,for early cure menthol rub introduced in market with high demand.This menthol rub was constituted as salve or ointment known as natural menthol rub suggested for common cold,marketed by newly established company Mentholatum,A USA based company(1889).Once the company launched they used to sell menthol rub as natural rub ointment consisting camphor.(It was made with less than 11 percent camphor and menthol with dissolved petroleum jelly was dissolved in it.Similarly,another company,Vicks comes into notice,in 1905 they manufactured and sell vicks vaporub(contains less than 5 % camphor in it)suggested to apply a small amount under the nose and on the chest,whereby vapours of camphor would be suggested to inhale continuously.In 1918 during Spanish flu time,vicks vaporub was in high demand and was tested to be remedy.The Spanish viral influenza almost killed 10 million people around the world.In USA,most of the citizens affected from it and around 50,000 died.The scenario was worst,whole USA standstill,hospitals were filled with over flow of patients and no remedy,no medicine discovered that time for viral and pneumonia[54].

During Covid-19 outbreak

In India,as a preventive measure against spread of COVID-19 in Homeopathy Camphora 1M is being recommended as a prophylactic given to personnel and staff of Maharashtra police as a homeopathic immunity booster.The medicine was given as an alternative medicine to the staffs of government department of Maharashtra police on the recommendation of Ministry of Ayurveda,Yoga &Naturopathy,Unani,Siddha and Homeopathy(AYUSH).As homeopathy medicines have no side effects,the consulted expert have said these medicine can be taken even if other allopathic treatment was under way[55].In the state of Hyderabad,the governor,who is also doctor,suggested camphor as a remedy for coronavirus,she shared the information socially “Look at the new drug to target SARS-CoV-2”.Compound identified is camphor,in traditional medicines Ayurveda;it has been used as a remedy.Camphor was used to fight plaque and influenza epidemics.According to old traditional practices pray with camphor or make Chakkarai pongal(sweet pongal)with Pacchai Karpooram(it is kind of variety of camphor with a white drug).The Hyderabad government has been an overwhelming support to the suggestion made by the Governor[56].In case of Homeopathic approach during pandemic or epidemics,the first approach is to follow preventive measures and provide interventions to keep the community enhanced and healthy.In Homeopathy the issues Genus epidemicus for immunity enhancement for the masses.The medicine recommended is “Camphora”.The medicine is selective and customized accordingly to consider each patients individual mental and physical conditions.In addition,if other illness also present in the case of age occupation,previous illness specific to the patient are taken into consideration.The famous quote of homeopathy suggests,“Homeopathy treats the patient but not the disease”.Both as preventive measures and treatment,the use of camphor recommended.Just similar like,the raw form of camphor drug has tremendous medicinal power.The presence of menthol in the camphor provides the cooling and sensation when applied to the skin of the body and act a mild pain reliever.Both menthol and camphor act together and can be used to relieve minor muscle and joint pain.Camphora medicine may also be used as a chest rub to sooth chest congestion problems,and relieve cough caused by the flu or common cold.It is also used in high-grade fever,headache,delusions,and paralysis case.It cures pneumonia by curing congestion of chest.Inability to rise due to weakness can also be cured by homeopathy Camphora medicine[57].As Homeopathy is an individualized system of therapy,therefore there is no possibility that one remedy will cure all cases of a specific pathology[58].However,for the symptoms of both respiratory and systematic homeopathy physicians uses ultra-high diluted solution of Camphor officinalis[59].

Conclusion

Hence the use of distinct form of camphor proven to be the cure of history of epidemics.In addition,at present of COVID-19 outbreak,camphor can act a preventive medicine for conventional system of medicine.It can act as new drug to target SARS-CoV-2 due to its high pharmacological activity.