ANTIMICROBIALS FROM NATURAL PRODUCTS USED AGAINST

RESISTANT STRAINS

SAPTARSHI SAMAJDAR16mphyto02

CENTRE FOR PHARMACEUTICAL SCIENCES AND NATURAL PDTS.

CONTENTS• INTRODUCTION• WHO REPORTS ON RESISTANCE• TIMELINE OF RESISTANCE• EPIDEMIOLOGY • MECHANISM OF RESISTANCE• NATURAL PRODUCTS USED AGAINST RESISTANT STRAINS• MECHANISM OF PHYTOCHEMICALS AGAINST RESISTANCE• DRUGS FROM NON PHYTOCHEMICAL SOURCES AGAINST

RESISTANCE• CONCLUSION• REFERENCES

INTRODUCTION• For last 60 years Antimicrobials have been a panacea to cure

infections.• But in 1945 in his Nobel Prize discourse, Sir Alexander Fleming

warned that these organisms will be impervious to antimicrobials in near future.

• Until 1970s new antimicrobials were developed rendering basic microbes defenceless. But from 80s developmental works have gone downwards.

• The main worry for resistance are:A. Increased mortality of human.B. Resistance may spread in groups.C. Added loads medical cost.D. Threat to go back to pre anti microbial period.

WHO REPORTS ON RESISTANCE

0

1

2

3

4

Respiratory infections HIV Diarrheal diseases Tuberculosis Malaria

Mill

ions

of d

eath

s, w

orld

wid

e, 1

998

S. pneumonia: Up to 55% resistance

to penicillin in some regions

HIV: Report of resistance to all

marketed agents

S. dyentariae: 90% resistance to

cotrimoxazole S.Typhi: Outbreaks of multi-

resistant strains in 11 countries

M. tuberculosis:Multi-drug resistant

tuberculosis

P. falciparum:Chloroquine resistance in

81/92 countries

Source: WHO

TIMELINE OF RESISTANCE

Source: http://www.icjournal.org/

EPIDEMIOLOGY

• First time reported in 1947 by Barber .• This lead to development of synthetic or semisynthetic

penicillin like methicillin.• By 1985 the susceptibility of Penicillin and its synthetic / semi

synthetic compounds increased from 20% to 85%• As per Italian epidemiology observation resistance is seen

more in adults than in children.• In India , most resistance are derived from nosocomial

source.

MECHANISM OF RESISTANCE

• HYDROLYSIS

• GROUP TRANSFER

• REDOX PROCESS

• MODIFICATION OF TARGET

• EFFLUX PUMP TECHNIQUE

NATURAL PRODUCTS USED AGAINST RESISTANT STRAINS

Casuarina: Biological source: From the leaves of Casuarina equisetifolia of family casuarinaceae. Geographical Source: Burma, Vanuatu, Queensland, North East India Chemical Constituents: Leaf contains mainly Pentadecanal and 1,8-cineole, with significant amounts of apiole , α-phellandrene and α-terpinene

Cineole Casuarina equestifolia Source (http://www.wikiwand.com/es/Casuarina_equisetifolia)

Sweet lemon: Biological Source : Obtained from the rind of Citrus sinensis of family Rutaceae

Geographical source: : Grown in all tropical countries, in India Kashmir, Himachal has rich tree content. Chemical Constituents: : Mainly Carmene, Targentin. Other than this atripliside B , beta-sitosterol are also present.

Targentin Citrus sinensis Source:www.pgpf.org

• Amla:• Biological source: Obtained from the fruits of Embelica officinalis of family

Combretaceae.• Geographical source: All over India especially in eastern region and it is grown

in different tropical and subtropical regions such as China, South-east Asia, Malaysia, Pakistan, Uzbekistan and Sri Lanka.

• Chemical constituents: Phyllantine, Kaempferol, Ascorbic acid, Chebulinic acid, Glutamic acid.

Kaemferol Embelica officinalis source: https://explorepharma.wordpress.com

• Henna:• Biological source: Obtained from the leaves of Lawsonia inermis of family

Lythraceae• Geographical source: The henna plant is native to northern Africa, western

and southern Asia, and northern Australasia, in semi-arid zones and tropical areas. Also grown in China, India, Sudan, Egypt and Caribbean Islands.

• Chemical Constituents: Lawsone is the active constituent of the Henna leaves. The other chemical constituents of Henna are gallic acid, white resin, sugars.

Lawsone Lawsonia inermis source: www.rarepalmseed.com

• Pomegranate• Biological source: Rind of Punica granatum of family Lythraceae• Geographical source: The pomegranate originated in the region of modern-day Iran,

and has been cultivated since ancient times throughout the Mediterranean region.• Chemical Constituent: Anthocyanins, glucose, ascorbic acid, ellagic acid, gallic

acid, caffeic acid, catechin, quercetin, rutin and numerous minerals particularly iron, amino acids. 

Ellagic acid Punica granatum source: http://www.dbrexportsindia.com

• Arjuna• Biological source: Obtained from the bark of Terminalia arjuna of family

Combretaceae.• Geographical source: Terminalia arjuna is native to India and Sri Lanka, but has

been planted as an ornamental tree throughout the tropical nations. In India , Uttar Pradesh, Madhya Pradesh, West Bengal and south and central India.

• Chemical Constituent: Main chemical constitutes are tannins, triterpenoid saponins (arjunic acid, arjunolic acid, arjunetin and arjunic acid), flavonoids, gallic acid, ellagic acid and phytosterols.

Arjunetin Terminalia arjuna source: WWF- India

MECHANISM OF PHYTOCHEMICALS AGAINST RESISTANCE

• Disintegration of cytoplasmic membrane,• Interaction with membrane proteins (ATPases and

others), • Disturbance of outer membrane of gram negative

bacteria with the release of lipopolysaccharides,• Destabilization of the proton motive force with leakage

of ions,• Coagulation of the cell content,• Inhibition of enzyme synthesis.

DRUGS FROM NON PHYTOCHEMICAL SOURCE

• BACTERIOPHAGE THERAPY:

CONT.• Using Nasutitermes corniger (Motchulsky) as adjuvant therapy: Extracts obtained from extract of nest as well as termites used against

resistant strains of S.aureus and E.coli has shown good result by decreasing substantial MIC values.

E.coli S.aureus

CONCLUSION

• In a situation where we have major chances of going back to pre antimicrobial era where natality will be very high.

• Before its too late we must find alternatives to stop it and natural product is one of them.

• Proper research with consideration of anthropological and ethnobiological aspects.

• There is also requirements of proper checking in every stage so that drugs of highest quality reaches patient.

REFERENCE• Organization, W. H. (2014). Global tuberculosis control 2014, World Health

Organization.• Chaves, T. P., Clementino, E. L., Felismino, D. C., Alves, R. R.,

Vasconcellos, A., Coutinho, H. D., & Medeiros, A. C. D. (2015). Antibiotic resistance modulation by natural products obtained from Nasutitermes corniger (Motschulsky, 1855) and its nest. Saudi journal of biological sciences, 22(4), 404-408.

• Ngwoke, K. G., Odimegwu, D. C., & Esimone, C. O. (2011). Antimicrobial natural products. Science agaianst microbial pathogens: communicating current research and technology advances. Badajoz, Spain: FORMATEX, 1011.

• Nascimento, G. G., Locatelli, J., Freitas, P. C., & Silva, G. L. (2000). Antibacterial activity of plant extracts and phytochemicals on antibiotic-resistant bacteria. Brazilian journal of microbiology, 31(4), 247-256.

• Ahmad, I., & Beg, A. Z. (2013). Antimicrobial and phytochemical studies on 45 Indian medicinal plants against multi-drug resistant human pathogens. Journal of ethnopharmacology, 74(2), 113-123.

• Pandit, R., Singh, P. K., & Kumar, V. (2015). Natural Remedies against Multi-Drug Resistant Mycobacterium tuberculosis. Journal of Tuberculosis Research, 3(04), 171.