Therapeutics values of plant derived compounds

Punyakishore Maibam

Quotation

“Within the infant rind of this small flower

Poison hath residence and medicine power:

For this, being smelt, with that part cheers each part;

Being tasted, slays all senses with the heart….”

(Romeo & Juliet Act II Scene III.)

Introduction

• Powerful ingredients.

• Only 15% of estimated plant species on earth have been investigated for possible Medicinal uses.

• No magic, diets high in fruits, grains, legumes reduce the risk of a various number of diseases

• More than 95 % of the population in the least developing countries use herbs for health and other purposes.

History

• History of traditional medicine in eastern culture– Ayurveda medicine– Chinese medicine

• History of traditional medicine in western culture– European history

The Greco-Roman Period The Dark ages 19th Century The 20th Century

– American history

• Breakthrough in pharmaceutical chemistry came when Serturner isolated morphine from opium poppy in 1806

Traditional Healing Systems

Ayurveda

The aim of Ayurveda

is proper maintenance of

metabolic equilibrium

of the human psychosomatic

material and the

restoration of the same to the

normal when disturbed

Contd…

• Ayurveda utilizes herbs and product from natural resources for healing

• Herbs like Neem , Aloe vera, Turmeric, Tulsi ( Holy basil), Babool, Garlic etc.

Chinese

• The Chinese believe that all things in creation possess the qualities of yin and yang, the opposing forces of nature

• When the balance between these two is lost, disease is manifest.

• Diagnosis is performed primarily through the pulse and tongue.

Unani

• Unani tibb meaning ‘Ionian’ or ‘Greek’ medicine

• based on the Greek tradition of four humours – blood, phlegm, black and yellow bile

Japanese

• Ancient Japanese medical practices involved exorcism, ritual bathing and herbal therapy

• kampo, using fewer and smaller quantities of herbs, often ground into granules to be taken in tea.

• It is the art of using the pure

essence extract to promote the

health and well-being of body

and mind.

• Relies primarily on the use of essential oils

• Common oils- lavender, eucalyptus, tea tree oil, neem, tulsi and cinnamon etc

Aromatherapy

Common plants used with its derived products

Plant family: Meliaceae

Plant used: Entire plant

Origin culture: Native to East India and Burma

Common uses: Antiviral, antifungal, antibacterial, antimalarial, antifertility, antiulcerogenic, antihypersensitive and antihyperglycaemic, antidermatophytic, orodontal, hepatoprotective and anticancer activity.

Active constituents: Diterpenoids, triterpenoids

(Azadirachtin), vilasinin type of compounds, limonoids and its derivatives.

Neem (Azadirachta indica)

Jungli amla (Phyllanthus amarus)

Plant Family: Euphorbiaceae

Parts used: Entire plant

Origin: South India

Common uses: Hepatitis, Gonorrhea, frequent menstruation, and Diabetes, anti-viral effect, skin for sores, swelling, and itchiness.

Active constituents: Phyllanthin D, hypophyllanthine and five flavonaoids viz. quercertin, astralgin, quercertrin, isoquercitrin and rutin.

Aloe vera

Plant family: Asphodelaceae

Part used: Leaf pulp

Origin culture: Sub-Saharan African and Coptic traditional medicine

Common uses: Treatment of burns, skin blemishes, topical irritations, antibacterial, digestive aid.

Active constituents: Anthroquinones, anthrols, anthrones, chrysophanic acid.

Garlic (Allium sativum)

Plant family: Alliaceae

.Part used: Leaves & stem (together called the bulb)

Origin culture: Chinese, Coptic, Farsi, Mediterranean, and Semitic traditional medicine

Common uses: Immunostimulation and augmented circulation, triglyceride and cholesterol level reduction, hypertension control.

Active constituents: Allicin, and allyl sulfides.

Ginger (Zingiber officinale)

Plant family: Zingiberaceae

.Part used: Rhizome

Origin culture: Chinese and

Indian traditional medicine.

Common uses: Digestive aid, carminative, nausea/vomiting remedy, anti-inflammatory.

Active constituents: Zingiberene, gingerols/shogoals (volatile oils).

Ginseng (Panax ginseng)

Plant family: Araliaceae

. Part used: Roots/rhizomes

Origin culture: Chinese, Korean, and Siberian traditional medicine.

Common uses: Taken internally for fatigue/endurance/stress, control high and low blood pressure.

Active constituents: Ginsenosides

Feverfew (Tanacetum parthenium)

Plant family: Asteraceae

Part used: Leaves

Origin culture: Mediterranean traditional medicine.

Common uses: Migraine headaches, fevers.

Active constituents: Parthenolide (a sesquiterpene lactose), tanetin.

Ginkgo (Ginkgo biloba)

Plant family: Ginkgoaceae

. Part used: Leaves

Origin culture: Chinese traditional medicine

Common uses: Improved memory, Alzheimer’s disease, Parkinson’s disease, improved circulation, post stroke recovery.

Active constituents: Ginkgolides/bilobalide and flavonoids

Milk Thistle (Silybum marianum)

Plant family: Asteraceae

.

Part used: Seeds

Origin culture: Mediterranean traditional medicine.

Common uses: Hepatitis, liver diseases.

Active constituents: Silymarin, silibinin, flavonoids.

St. Johns Wort(Hypericum perforatum)

Plant family: Clusiaceae

Part used: Flowers & upper stems/leaves

Origin culture: Greek traditional medicine.

Common uses: Antidepressant, Antiviral.

Active constituents: Volatile oil, carotenes, taninnin, flavanoids (inc. hypericin)

To make it more effective and commercialized…

Principal concepts of research on new medicines(Kuo-Hsiung Lee, 2005)

New approach

• Biotransformation:

The chemical conversion of an exogenously supplied substance by living cell cultures, permeabilzed cells or entrapped enzymes derived from cell culture.( Yeoman et al., 1990)

• Single step or multiple step

• A method used to improve the product yield.

Production of digitoxin• Cardiac glycosides from Digitalis species for heart

diseases• Yeild from D. lanuta & D. purpurea were low.• Progesterone added for yield

g%

-Methyldigitoxin added

Unconverted -methyldigitoxin

-Methyldigoxin formed

By-product

Yield

17.24 (100)

2.0 (11.8)

14.36 (81.7)

0.28 (1.4)

(94.90)

Biotransformation of -methyldigoxin by D. lanata cells in 201 bioreactor over a period of 17 days

(Misawa, 1994)

Drawbacks

Drawbacks

• Toxicities are not well defined in herbal medicine

• Risk of overdose is higher

• Too much believe in herbal therapy

• Herbs and other alternatives therapies are more likely to abandon potentially beneficial conventional therapy when faced with an illness.

Reported Adverse Effects of Some Common Herbs (Winslow et al., 1998)

Case studies

Introduction

• Two most dreadful diseases

• Plants have formed the basis of sophisticated traditional medicine systems that have been in existence for thousands of years in countries, such as China (Chang & But, 1986) and India (Kapoor, 1990).

• Plant-derived compounds have played an important role in the development of several clinically

useful anti-cancer and anti-aids agents.

Plant- Derived Anti Cancer agents

First agents, vinca alkaloids (vinblastine and vincristine) from the Madagascar periwinkle, Catharanthus roseus (Cragg et al., 1994)

• Epipodophyllotoxin used as the active anti -tumour agent from the genus Podophyllum (Cragg et al., 1994)

• Most recent additions are Paclitaxel (Taxus brevifolia), campothecin (Camptotheca acuminata) homoharringtonine (Cephalotaxus harringtonia var. Drupacea), elliptinium, a derivative of ellipticine (Bleekeria vitensis), combretastatins, (Combretum caffrum)

Contd…• The leaves of T. baccata are used in the traditional Asiatic

Indian (Ayurvedic) medicine system (Kapoor, 1990), with one reported use in the treatment of .cancer. (Hartwell, 1982)

• Homoharringtonine against various leukemias while elliptinium for the treatment of breast cancer (Cragg et al., 1993b).

• The combretastatins (Combretum caffrum) which act as anti-angiogenic agents, causing vascular shutdown in tumours (Holwell et al., 2002).

Anti- HIV agents• Michellamine B isolated from the leaves of the liana,

Ancistrocladus korupensis, (Boyd et al., 1994).

• Calophyllum lanigerum, yielded calanolide A which showed significant anti-HIV activity (Kashman et al., 1992)

• Prostratin from Homalanthus nutans (Gustafson et al., 1992) determined that prostratin is a potent activator of HIV expression in latently infected T-cell lines

• Extracts of the Smokebush (Conospermum incurvum) yielded conocurvone as the active agent (Decosterd et al., 1993)

Introduction

• Aim of the study: To study the production of cinnamyl alcohol glycosides by biotransformation

• Rhodiola rosea is only the species that produce he cinamyl alcohol glycosides

• Various secondary metabolites are the cinnamyl alcohol glycosides (rosin, rosavin, rosarinand) & tyrosol and its glycoside salidroside

• Field cultivation takes several year so cell and tissues cultures give a satisfactory results

• Apart other compounds 337, 481, 483, and 321 are also reported (Tolonen et al., 2004)

•

•

Biosynthetic pathway of A) rosin, rosavin, rosarin and B) salidroside.

Biosynthetic pathway of salidroside and cinnamyl alcohol glycosides

(A) (B)

Materials and methods

Experimental material

Experiment with the precursors

Fresh and dry weight measurements

Chemical analyses high performance liquid chromatography

with mass spectrometric detection

Results and discussion

• Growth of the cultures

• Production of the cinnamyl alcohol glycosides Addition of glucose was beneficial concerning

the production Rosin production increased Rosavin was not produced in the original

medium

• Production of salidroside

• Addition of glucose to the medium show any positive effect

• Accumulation pattern was same in both cases

Contd…

The content of salidroside in the callus cultivated with 2 mM tyrosol in the original MS-Rh medium (containing only sucrose) or in the glucose containing medium, during 14 days.

The content of rosin and rosavin in the callus cultivated with 2 mM cinnamyl alcohol in the original MS-Rh medium (containing only sucrose) or in the glucose containing medium, during 14 days.

(Gyorgy et al., 2005)

Pharmacological effects of the alcohol-aqueous extract of Rhodiola rosea(Gyorgy et al., 2006)

Conclusion

• Production of rosin and rosavin can be increased by biotransformation

• Ultimately leads to satisfactory content of the pharmacologically interesting compounds

Introduction

• Aim of study To study the anti-ulcer and ulcer-healing activity of OS.

• OC leaves 0.7% volatile oil comprising about 71% eugenol and 20% methyl eugenol.

• Additional components are carvacrol, sesquiterpine hydrocarbon caryophyllene, apigenin, luteolin,apigenin-7-O-glucuronide, orientin, molludistin and ursolic acid (Gupta et al., 2002)

Materials and methods

Control:

OS extract and standard anti- ulcer drug Omeprazole (OMZ)

Treatment:

OS extract and OMZ

Ulcerogens• Cold restraint stress induced ulcers

(CRU)• Aspirin-induced ulcers (ASP)• Alcohol-induced ulcers (AL)• Histamine- induced ulcers (HST)

• Pylorus ligation-induced ulcers (PL)

• Animals (rats/guinea pigs)– Anti-ulcer study(6 rats\6

guinea pigs)– Ulcer healing study (20

rats/20 guinea pigs)-acetic acid- induced ulcer model.

• Treatment schedule

• Evaluation of ulcer-healing activity- acetic acid- induced ulcer model

3 days

Results

Effect of ethanolic extract of Ocimum sanctum and omeprazole at doses of 50, 100 and 10 mg/kg body weight,

respectively, on percentageprotection of ulcer index in different anti-ulcer models.

Effect of ethanolic extract of Ocimum sanctum and omeprazole at doses of 100 and 10 mg/kg body weight

per day, respectively, on percentageprotection of ulcer index in acetic acid-induced ulcer

model in rats after 5, 10, 15 and 20 days of drug treatment.

(Dharmani et al., 2004)

Histopathology of acetic acid-induced ulcers

Sections of ulcerated stomach obtained from rats of control groups and treated with Ocimum sanctum in acetic acid-induced ulcer model in

ratsafter 5 days of treatment

C T

C T

C T

Sections of ulcerated stomach obtained from rats of control groups and treated with Ocimum sanctum in acetic acid-induced ulcer model in

ratsafter 10 days of treatment

Sections of ulcerated stomach obtained from rats of control groups and treated with Ocimum sanctum in acetic acid-induced ulcer model in

ratsafter 15 days of treatment

(Dharmani et al., 2004)

• Report suggests that anti-stress and anti-oxidant activity of OS which suggests the free radical scavenging effect of OS (Sen et al., 1992).

• Ethanol induced ulcers are due to direct necrotizing effect of ethanol on gastric mucosa (Miller and Henagan, 1984) so OS increases mucus secretion.

• In PL, ulcers are developed due to accumulation of gastric acid and pepsin which leads to auto-digestion of gastric mucosa (Goel and Bhattacharya, 1991).

Discussion and conclusion

Conclusion

Doubts please !!!

Thank you