Therapeutics values of plant derived compounds
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Therapeutics values of plant derived compounds
Punyakishore Maibam
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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.)
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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.
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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
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Traditional Healing Systems
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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
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Contd…
• Ayurveda utilizes herbs and product from natural resources for healing
• Herbs like Neem , Aloe vera, Turmeric, Tulsi ( Holy basil), Babool, Garlic etc.
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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.
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Unani
• Unani tibb meaning ‘Ionian’ or ‘Greek’ medicine
• based on the Greek tradition of four humours – blood, phlegm, black and yellow bile
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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.
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• 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
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Common plants used with its derived products
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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)
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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.
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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.
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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.
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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).
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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
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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.
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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
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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.
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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)
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To make it more effective and commercialized…
Principal concepts of research on new medicines(Kuo-Hsiung Lee, 2005)
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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.
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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)
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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.
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Reported Adverse Effects of Some Common Herbs (Winslow et al., 1998)
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Case studies
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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.
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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)
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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).
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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)
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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)
•
•
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Biosynthetic pathway of A) rosin, rosavin, rosarin and B) salidroside.
Biosynthetic pathway of salidroside and cinnamyl alcohol glycosides
(A) (B)
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Materials and methods
Experimental material
Experiment with the precursors
Fresh and dry weight measurements
Chemical analyses high performance liquid chromatography
with mass spectrometric detection
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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
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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)
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Pharmacological effects of the alcohol-aqueous extract of Rhodiola rosea(Gyorgy et al., 2006)
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Conclusion
• Production of rosin and rosavin can be increased by biotransformation
• Ultimately leads to satisfactory content of the pharmacologically interesting compounds
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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)
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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
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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)
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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)
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• 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
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Conclusion
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Doubts please !!!
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Thank you