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Monday, June 17, 2013

Scientific Basis for Ayurvedic Therapies -9
















































































Scientific Basis for
Ayurvedic Therapies 


edited by
Brahmasree Lakshmi Chandra Mishra







7.6 Therapy (Chikitsa)

DM patients. Traditional daily management of DM is carried out with appropriate palliative
herbal therapies. These herbs are selected based on their properties, such as rasa (taste),
guna (physicochemical properties), veerya (potency), vipaka (postdigestive effect), and prabhava
(unique action), that are necessary to bring about balance in dosas. On the basis of
this approach, Charak Samhita has prescribed the following palliative treatments specific
for dosa constitutions: 10 water decoctions for kapha, 10 decoctions for pitta, and 1 ghee
for vata in which 17 herbs are collectively cooked.4,13
TABLE 7.2
Decoctions to Treat Pittaja Pramehas
Medicinal Plant Botanical Name Medicinal Plant Botanical Name
Decoction #1 Decoction #6
Usira Vativeria zizanoides Linn. Nimba Azadirachta indica A.
Lodhra Symplocos cocchinchinensis Arjuna Terminalia arjuna
Arjuna Terminalia arjuna Guduchi Tinospora cordifolia
Candana Santalum album Linn. Haridra Curcuma longa
Utpala Nymphaea stellata
Decoction #2 Decoction #7
Usira Vetiveria zizanoides Linn. Sirisha Albizia lebbek
Musta Cyperus rotundus Sarja Vateria indica Linn.
Amalata Cayratia trifolia Arjuna Terminalia arjuna
Abhaya Terminalia chebula retz Nagakesar Mammea suriga
Decoction #3 Decoction #8
Patala Cydonia oblonga Priyangu Aglaia elaeagnoidea
Nimba Azadirachta indica A. Kamala Nelumbo nucifera
Amalaka Embilca officinalis Geartn. Utpala Nymphaea stellata
Gudici Tinospora cordifolia Miers. Palasha flower Butea monosperma
Decoction #4 Decoction #9
Musta Cyperus rotundus Asvattha Ficus religiosa
Haaritaki Terminalia chebula Patha Stephania japonica Miers
Padmaka Prunus cerasoides D. Asana Pterocarpus marsupium
Kutaja Holarrhena antidysenterica wall. Vetasa Salix caprea Linn.
Decoction #5 Decoction #10
Lodhra Symplocos cocchinchinensis Daruharidra Berbers aristata
Hribera Coleus vettiveroides Jacob Utpala Nymphaea stellata
Kaliyaka Coscinium fenestratum Muskaka Schrebera swietenioides
Dhataki Woodfordia floribunda Salish
Note: The decoctions are useful in all types of pramehas. They can be used as impregnated on barley,
food, or drinks.
These herbs are listed in Tables 7.1
The principles of Ayurvedic therapy as discussed in Chapter 2 are also applied to treat
to 7.4.

It is important to note that vigorous exercise is contraindicated in lean and weak patients
with severe diabetes. They are advised to perform yoga and breathing exercises (pranyama).
In fact, certain yoga practices and breathing exercises are believed to stimulate better
utilization and production of insulin by stimulating both the pancreas and muscles. Other
lifestyle changes recommended are regular walking and reducing the consumption of fatproducing
foods such as lard, butter, and oils. The use of bitter gourd, pungent- and
astringent-tasting food, asparagus, spinach, turmeric, fenugreek seeds, black pepper, and
ginger is encouraged in the diet. Current experience suggests that it is unnecessary to
exclude the use of sucrose, provided it is consumed in balance with a normal diet2 that
is consistent with Ayurvedic recommendations. Honey and jaggery are believed to pacify
kapha and pitta, respectively, and may be useful in respective DMs. Patients are also asked
to stop smoking tobacco, eliminate alcohol consumption, and restrict sleeping time to
about 8 h/day.
Individual herbs are generally not used in Ayurvedic therapies. Because therapies are
based on a predominant dosa and body constitution, they always include formulas containing
many herbs and sometimes various minerals. In Ayurveda, every disease has one
or two predominant dosas that need to be balanced according to the constitution of the
patient; therefore, one therapy may not be applicable to all patients even though the
patients share the same disease. Some of the formulations commonly used to treat type 2
the treatment of DM type 1 patients in order to help in decreasing their reliance on this
hormone.
Ayurveda recommends that the patient’s lifestyle, age, type of work, psychosocial needs,
and will power are considered in a management plan. The latter includes the necessary
panchkarmas, herbal formulas, a healthy meal plan, and blood-sugar monitoring. A physician
needs to evaluate the plan at each visit and make necessary modifications.
Ayurvedic physicians currently monitor conventional blood sugar levels in the management
of DM. The goal is to keep the premeal glucose level within 80 to 110 mg/day,
bedtime glucose level within 100 to 140 mg/day, the low density lipid cholesterol (bad)
at <100 mg/day, and the high density lipid cholesterol (good) above 35 mg/dL.2
The preventive measures for DM are primarily the adoption of life style and food habits
that reduce fat accumulation in the body, because 80% of type 2 DM patients are known
to be obese. Regular use of rasayanas and hypoglycemic herbal formulas may be useful as
a preventive measure, particularly for those who have a family history of type 2 diabetes.
7.7 Scientific Basis
Buanides and sulfonylureas, discovered in the 1920s and 1940s, respectively, are still the
most frequently prescribed hypoglycemic agents, although Ciglitazone, Pioglitazone, alphaglucosidase
inhibitors, and others are available.3 In an 8-year large multicenter clinical trial
conducted by the University Group Diabetes Program (UDGP), patients treated with tolbutamide
suffered a twofold increase in mortality as compared with insulin-treated patients.14
The study has not been completely refuted and physicians continue to treat patients with
oral hypoglycemic agents, including tolbutamide, because there are few choices available
to patients other than insulin where they are resistant to dietary and lifestyle changes.3
Ayurvedic therapies for DM are effective in controlling blood-sugar levels, either given alone
or as an adjunct with other hypoglycemic drugs or insulin. Ayurveda offers alternative
DM are listed in Table 7.5. These formulas may also be used concurrently with insulin for

choices to control type 2 DM. Our literature search has revealed more than 52 herbs that
frequently used in Ayurvedic formulas. Studies on six herbs and seven formulas are presented
to demonstrate the scientific basis of the Ayurvedic therapies of DM.
7.7.1 Gymnema sylvestere R.Br. (Asclepiadacea)
Gymnema sylvestere (GS), a plant popularly known as gurmara (meaning sugar destroyer),
is derived from a large woody climber that grows in the hills of Behar, Orissa Madhya
Pradesh, and the Deccan Peninsula of India. It has been used in Ayurveda to treat DM
for 2000 years. The whole plant, seeds, leaves, and roots are taken as a powder or as a
decoction in combination with other herbs. The alcohol extract of GS (known as GS4)
contains gymnemic acids (a chemically complex mixture of saponins and gurmarin, a
polypeptide of 35 amino acids).15
TABLE 7.3
Group of Herbs To Treat Vataja Pramehas
Medicinal Plant Botanical Name
Goksura Tribulus terrestris
Asmantaka Mulaka parna (ARU) Ficus cordifolia
Roxb.
Somavalka Acacia suma Kurz
Bhallataka Semecarpus anacardium
Ativisa Aconitum heterophyllum
Lodhra Symplocos cocchinchinensis
Vaca Acorus calamus
Patala Stereospermum suaveolens DC
Arjuna Terminalia arjuna
Nimba Azadirachta indica A.
Musta Cyperus rotundus
Haridra Curcuma longa
Padmak Prunus cerasoides
Yavani Carium copticum Benth
Manjistha Rubia cordifolia Linn.
Aguru Aquilaria agalloocha Roxb.
Candana Santalum album Linn.
Note: Herbs should be collectively cooked in oil for kapha-vataj
or ghee for pitta-vataja.
TABLE 7.4
Herbs to Treat Kapha-Vataja Pramehas
Medicinal Plant Botanical Name
Kampillaka Mallotus philippinensis
Saptacchada Alstonia scholaris R.
Sala Shorea robusta Geratn
Bibhitika Terminalia bellirica
Rohitka Aphanamixis polystachya
Kutaja Holarrhena antidysenterica Linn.
Kapittha Limona elephantum
Note: Herbs can be taken as powder or paste in the dose of 10 g.
have been shown to have hypoglycemic activity (Table 7.6). Some of these herbs have been

TABLE 7.5
Ayurvedic Formulas
Formula Dose (per day) Ref.
Kaisora guggul 3 g AFa Section 5:2
Dhanvantra ghrat 12 g AF Section 6:22
Navayasa churn 1–3 g AF Section 7:17
Nyagrodhadi churn 1–3 g AF Section 7:21
Traikantaka ghrat 12 g AF Section 6:15
Vastyamayantaka ghrat 12 g AF Section 6:40
Shatavaryadi ghrit 12 g APb Part II
Agnitundi bati 125 mg twice Bhasahya Ratnavali
Madhumehar yog 1 tablet twice Ayurveda Sar Sangraha
Shilajatwadi bati 1 pill twice Bhasajya Ratnavali
Ayush-82 5 g 3 times 104, 105
Abraga chenodooram 200 mg twice 108
D-400 2 tablets 3 times 109
MA 471 500 mg twice 106
Sandana Podia (Siddha formula) 300 mg twice 110
Kadal Azhinjil choornam (Siddha formula) 500 mg twice 111
M-93 1 g 112
aAF = Ayurvedic Formulary of India (Government of India publication).
bAP = The Ayurvedic Pharmacopoeia of India (Government of India publication).
TABLE 7.6
Scientific Studies on Hypoglycemic Herbs
Plant Name Ref. Plant Name Ref.
Acacia arabica 113 Momordica charantia See text
Achyranthes aspera 114 Momordica cymbalaria 162, 163
Aegle marmelos 115, 116 Mucuna pruriens 164, 150
Allium cepa 117–119 Murraya koengii 165
Allium sativum 120–125 Musa sapientum 166–168
Aloe vera 126–130 Nelumbo nucifera 169
Andrographis paniculata 131, 132 Ocimum sanctum 134, 170–172
Azadirachta indica 133–136 Phaseolus mungo 173, 174
Bombax ceiba 137 Phyllanthus amarus 175
Caesalpinia bonducella 138 Phyllanthus urinaria 176
Calendula officinalis 139 Picrorrhiza kurroa 177
Capparis decidua 140 Polygonatum officinale 178
Capsicum frutescens 141 Psidium guajava 179
Cassia fistula 142 Pterocarpus marspium See text
Catharanthus roseus 134, 143 Pterocarpus santalinus 180
Coccina indica See text Punica granatum 181
Colocassia esculenta 144 Swertia chirayita 182–187
Cryptostegia grandiflora 145 Syzygium alterniffolium 188
Cyamopsis tetragonoloba 146, 147 Tecoma stans 189, 190
Eugenia jambolana 148–152 Teramus labialis 191
Ficus bengalonsis See text Tinospora cordofilia 150, 152 192, 193
Ficus carica 153, 154 Tinospora crispa 194–196
Gymnema sylvestre See text Trigonella foenumgraecum See text
Hamiltonia suaveolens 155 Vinca rosea 197
Hibiscus rosa-sinensis 156–158 Withania somnifera 198
Inula racemosa 159
Mangifera indica 160, 161

7.7.1.1 Animal Studies
Hypoglycemic activity and mechanism of action of GS have been examined in many
animal studies. The following data offer possible mechanisms by which GS might exert
its hypoglycemic effect:
1. Increase in the secretion or release of insulin — GS has been shown to stimulate
secretion or release of the insulin in vivo and in vitro.16–21
2. Protection of the pancreas from chemical toxins — GS has been shown to have
partial protective effect on the pancreas against potent pancreatic toxins like
beryllium.22 It also has been suggested that GS may be promoting the regeneration
of islet cells destroyed by streptozotocin in rats.23,24 Al-DM rats treated with GS
lived longer than the untreated diabetic rats, further supporting the regeneration
hypothesis.25
3. Increased utilization of glucose — GS has been shown to increase the activities of
enzymes responsible for the utilization of glucose by insulin-dependent pathways,
an increase in phosphorylase activity, and a decrease in gluconeogenic enzymes
and sorbitol dehydrogenase.17
4. Inhibition of glucose absorption from intestine — GS has been shown to inhibit
the absorption of glucose from the intestine.26
7.7.1.2 Clinical Studies
Several clinical studies have been done to help authenticate the hypoglycemic effect of
Our literature search has found two case control studies and two smaller studies. Major
drawbacks in these clinical trials are small sample size and inadequate study duration.
1. One group (n = 10) of 4 normal healthy females and 6 males (ages 19 to 25)
(nondiabetic) and another group (n = 6) of 2 females and 4 males (ages 35 to 50)
(type 2 DM) were studied for the antidiabetic effect of GS.27 Diabetic patients were
given an aqueous decoction of shade-dried GS leaves in a dose of 2 g 3 times/
day for 15 days and healthy subjects were given the same dose for 10 days. The
fasting blood sugar (FBS) (mg/day) was measured at 30 min postprandial blood
sugar (PPBS) and at 2 h PPBS on day 1 before the treatment and on day 10 after
daily treatments. Healthy subjects showed mean blood sugar levels of 80, 156,
and 76 on day 1 and 69, 132, and 66 on day 10, respectively. Those in the diabetic
group showed blood sugar levels of 135, 220, and 152 on day 1 and 110, 180, and
121 on day 10, respectively. Authors concluded that GS treatment demonstrated
a blood sugar lowering effect in both normal and diabetic subjects.27
2. Eight type 2 DM patients were treated with 10 g of GS leaf powder orally daily
for 21 days. The study showed significant reduction (p < 0.05) in blood sugar
levels, mean fasting BGL, and mean 2-h BGL as compared with baseline.28
3. GS4, a water-soluble acid fraction of an alcoholic extract of GS, was supplemented
in diet to a group of 22 diabetic type 2 patients.24 These patients were given oral
hypoglycemic therapy plus GS4 (400 mg/day) for 1 to 12 years (mean = 4.6 years).
A second group of 25 type 2 DM patients was given only hypoglycemic therapy
alone for 1 to 5 years (mean = 2.7 years). Group 1 showed significant improvement
(p < 0.001) in blood sugar cholesterol and triglycerides levels, whereas group 2
showed fewer effects compared with group 1 (p < 0.001). Patients in group 1
GS. These studies are evaluated based on the considerations outlined in Chapter 3.

developed symptoms of hypoglycemia and the dose of their hypoglycemic agents
had to be changed or stopped. The authors suggested that GS supplementation
showed an obvious advantage over conventional hypoglycemic therapy alone.24
4. Another study23 done on GS4 reported a synergistic effect of this GS extract on
BGLs in 23 type 1 diabetic patients (ages 10 to 31) who continued on insulin
therapy plus GS4 as compared with 37 type 1 diabetic patients (ages 8 to 30)
who were on insulin therapy alone. The dose of GS4 was 400 mg/day for 6 to
8 months. All patients in the combination therapy developed hypoglycemia and
their insulin dose had to be reduced. Insulin doses, fasting glucose, hemoglobin
A1c, cholesterol, triglycerides, and free fatty acids were reported for the longest
follow-up intervals. Although this study had many design problems, the data
derived from it were somewhat encouraging. In fact, the authors concluded that
GS4 improved blood glucose homeostasis and showed a better control of hyperlipidemia.
23
7.7.2 Momordica charantia (Cucurbitaceae)
Momordica charantia (MC), a climbing vine, has been widely used in Ayurveda as an
antidiabetic, abortificient (whole plant), antirheumatic, and carminative (fruits) agent. It
is believed to cure deranged kapha and pitta.29 The gourd produced by the plant, known
as karela in India (bitter gourd), is traditionally eaten as a fried vegetable or as a fresh
juice. Pharmacological and clinical studies demonstrating the hypoglycemic activity of
MC are summarized here.
7.7.2.1 Animal Studies
The hypoglycemic activity, mechanism of action, and toxicity of MC have been extensively
investigated in streptozotocin-induced or alloxan-induced DM (SZ-DM or AL-DM) rat
models.30–44
Oral feeding of MC at 200 mg/kg/day for 40 days prevented renal hypertrophy as
compared with SZ-DM in treated control rats, indicating that MC may have a protective
effect against renal toxins.45 Morevoer, an active hypoglycemic agent, polypeptide-p, with
a minimum molecular weight of approximately 11,000 (166 residues), was isolated from
fruits, seeds, and tissues of MC. The agent was very effective when administered subcutaneously
to gerbils, langurs, and humans in reducing blood sugar levels.31 MC extracts
were also studied in relation to the course of the development of eye cataracts, one of the
major side effects of DM. In fact, MC fruit extract given 4 g/kg/day for 20 days to ALDM
rats delayed the cataract formation by 2 months as compared with untreated diabetic
rats. Blood sugar level in the diabetic control rats was 307 mg/day compared with 149
mg/day in the diabetic-treated rats. These findings suggest that the protective effect may
be dependent upon the maintenance of lower BGLs.46
The mechanism of the antidiabetic action of MC has been studied extensively. Fractionation
extraction studies using alkaline and acid wash of chloroform extract of MC have
shown that the alkaline wash residue produced a hypoglycemic effect 1 h after administration
in SZ-DM rats. This same effect was much slower to occur with the residue from
the acid wash.34 On the basis of these results, authors stated that MC may be acting partly
via pancreatic and partly via extrapancreatic mechanisms.

7.7.2.1.1 Increase in Secretion or Release of Insulin
The increased secretion or release of insulin as a mechanism of the hypoglycemic activity
is supported by several studies.33,35,41 These studies indicate that MC increases (regenerates)
or possibly facilitates the recovery of pancreatic beta cells and that viable beta cells in the
pancreas that are capable of secreting insulin are still necessary for MC to exert its hypoglycemic
effect. Other biochemical effects, such as the reduction in lipid peroxidation reported
in SZ-DM rat pancreas and islet cells,43 may be contributing to MCs hypoglycemic activity.
7.7.2.1.2 Decreased Synthesis and Increased Utilization of Glucose
Biochemical studies done on MC have shown that hepatic glucose-6-phosphatase and
fructose-1,6-biphosphatase activities are increased and hepatic glucose-6-phosphate dehydrogenase
activity is decreased by streptozotocin in SZ-DM rats.36 MC treatment of SZDM
rats depressed the phosphatase activities and enhanced the dehydrogenase activity,
resulting in depressed synthesis and increased oxidation of glucose, respectively, leading
to lowered blood sugar levels. In a comparative study with oral hypoglycemic drugs, MC
treatment caused 10 to 15% reduction in BGL, whereas tolbutamide caused 40% reduction
in BGL 1 h postadministration.37 The effect of MC was not accompanied by increased
insulin secretion. In SZ-DM rats, MC caused 26% reduction in BGL, whereas metformin,
a biguinide, caused 40 to 50% reduction. MC increased the rate of glycogen synthesis in
the liver by four- to fivefold as detected by the incorporation of 14C-glucose into glycogen;
this suggests that increased glucose utilization in the liver may be a more important
mechanism of action of MC.
7.7.2.1.3 Inhibition of Intestinal Glucose Absorption
It has been suggested that the inhibition of glucose uptake from the intestine may be an
important factor in lowering BGL by MC.40 Two hypoglycemic chemical constituents were
isolated from the plant: (1) the oleanolic acid 3-O-monodesmoside, momordin Ic, and (2)
oleanolic acid 3-O-glucuronide. These chemicals showed a dose–response effect in inhibiting
the increase in serum glucose levels in oral glucose-loaded rats, but showed no
significant effect on serum glucose levels in normal rats, intraperitoneal glucose-loaded
rats, or AL-DM mice. Both chemicals were also found to suppress gastric emptying time
in rats, in addition to inhibiting glucose uptake in rat’s small intestine in a dose-dependent
manner in vitro. These results indicate that these chemicals have neither insulin-like activity
nor insulin-releasing activity; they apparently inhibit glucose absorption by suppressing
the transfer of glucose from the stomach to the small intestine and by inhibiting the
glucose transport system at the small intestine brush border. Inhibition of gastric emptying
is, at least in part, mediated by capsaicin-sensitive sensory nerves and the central nervous
system.42
7.7.2.1.4 Decrease in Insulin Resistance
A decrease in insulin resistance is also a possible mechanism of action for MC. In fact, a
significant increase in the muscle content of facilitative glucose transporter isoform 4
(GLUT4) protein content was found in the plasma membrane of KK-Ay mice, an animal
model for type 2 diabetes, after 3 weeks of oral administration of MC. This increase in
receptors induced by MC was postulated to be a contributing factor to the lowered insulin
resistance in these mice.39

7.7.2.1.5 Biochemical Effects of MC
Daily MC fruit extract feeding over a period of 10 weeks was found to reverse the increase
of malonedialdehyde, a plasma lipid peroxidation (LPO) product, and LPO in kidney,
nonesterified cholesterol, triglycerides, phospholipids, and high density lipoprotein
(HDL)-cholesterol in the blood of SZ-DM rats.44 These biochemical effects may account
for the hypolipidemic action of MC.
Other biochemical studies demonstrated the effect of MC on hepatic drug-metabolizing
enzymes. One expample is the reversal of a 50 to 100% increase in hepatic anilin hydroxylase
(AH) and ethoxyresorufin-O-deethylase (EROD) activities in SZ-DM rats after MC feeding.
In addition, a decrease (17 to 20%) in aminopyrene N-demethylase (ADP) activity and
cytosolic glutathionone concentration in SZ-DM rats was brought to normal, and ethoxycoumarin-
O-deethylase (ECOD) was even further decreased to 60% of control values by
MC. This latter finding was not shown to consistently reverse the effects on drug-metabolizing
enzymes in SZ-DM rats. This finding is probably due to the changes in hepatic
phase 1 and phase 2 drug-metabolizing enzyme levels in SZ-DM animals and may be
associated with the altered gene expression of different citochrome P450 (CYP) and glutathione
transferase isozymes.38 Another theory suggested that the altered metabolism of
endogenous substrates and hormonal status in DM may be responsible for changes in the
metabolism and oxidative stress in various tissues.47
7.7.2.2 Clinical Studies
An insulin-like compound isolated from MC was delivered by injection to 8 male and 1
female patients (ages 16 to 52) and to 5 healthy normal control subjects of the same age
range for a period of 3 months to 5 years. The compound produced a consistent hypoglycemic
effect in a small number of both type 1 and type 2 patients.48 In another study, 50
mg/kg of MC powder was administerd twice a day for 7 days to 8 type 2 DM patients
(ages 38 to 50). A significant (p < 0.001) hypoglycemic effect was also noted in these
patients.49
Another MC investigation was performed on 9 type 2 DM patients who were allowed
to continue on oral hypoglycemic drugs, but were asked to stop the drug 48 h before the
glucose tolerance tests. The results showed that the water extract of MC caused a significant
reduction in BGLs during the 50-g oral glucose tolerance tests when compared with
controls. Insulin levels were statistically higher with MC juice, but no effect on insulin
was seen in patients eating fried MC fruits with food.30 A follow-up to this study by the
same authors investigated MC juice and fried MC fruit in 9 type 2 diabetic patients. The
patients were treated for 8 to 11 weeks. They took 50 ml of the juice or 230 g of the fried
fruit, along their regular oral hypoglycemic agents, but were asked to stop their intake 48
h before the glucose tolerance tests. The authors reported that MC taken as a juice or as
fried fruits showed significant hypoglycemic activity.30
The fruit juice of MC significantly improved the glucose tolerance of 73% of the patients
under investigation in one study;50 a decoction of MC fruit in 200 ml of boiling water,
given 100 ml/day for 3 weeks, produced a significant decrease in hemoglobin A1c from
8.37 to 6.95% in another study.50 A dose of dry MC fruit powder, 5 g/day for 3 weeks, did
not lower blood sugar significantly. Drinking the aqueous suspension of MC fruit pulp
also led to a significant (p < 0.001) reduction of both FBS and PPBS levels in 86% of the
cases studied out of a 100 moderate type 2 DM patients.52 A significant hypoglycemic
activity was observed in 7 type 2 DM patients treated with MC aqueous extract (100 g of
the fruit boiled in 200 ml of water, dose of 100 ml) given orally daily for 3 weeks.51

As can be deduced from the above data, the results shown in clinical studies are
consistent with those obtained from the preclinical studies. This evidence provides a
relatively adequate scientific basis for the use of MC in Ayurvedic therapies of DM.
7.7.3 Trigonella foenum-graecum Linn. (Leguminose Family)
Trigonella foenum-graecum (TF), known as methika in Hindi and Sanskrit and methi in Tamil,
is an erect aromatic herb, 30 to 50 cm tall.53 It is widely cultivated in many parts of India.
Its seeds are used in cooking as well as treating diabetes, whereas its leaves are eaten as
a vegetable. The endosperm of the seed is rich in galactomannan (14 to 15%), young seeds
contain carbohydrates and sugar, and mature seeds yield amino acids and fatty acids on
hydrolysis. TF seeds also contain carotene, vitamins, and saponins.53 It is used in Ayurveda
as a diuretic, tonic, carminative, astringent, and emoliant. It is also used to treat diabetes,
colic, dysentery, diarrhea, coughing, dropsy, rheumatism, rickets, and anemia and to
subdue deranged vata.53
The antidiabetic activity of TF has been confirmed in both animal models54–64 and type
2 DM patients.65,66 The hypoglycemic effect of TF has been shown to reside in the defatted
seed material. A clear decrease in hyperglycemia and glycosurea and a decreased hyperglycemic
effect in an oral glucose tolerance test in TF-treated AL-DM dogs have been
shown.67 The effect was found in the fraction “a” of the defatted portion of the TF seed
that contains testa and endosperm and is rich in fibers (79.6%). The fraction “b” that
contains the cotyledons and axes and is rich in proteins (52.8%) did not show the effect.
It was also found that saponins isolated from TF seeds enhance food consumption and
the motivation to eat and reduce plasma cholesterol levels in rats.68 It was also postulated
that the hypoglycemic activity of TF is not concentrated in any one TF consitituents based
on the retention of this activity in all TF parts such as the seed powder, methanol extract,
and the residue remaining after the methanol extraction.58 Chemical analysis of the water
extract of the methanol extractive-free residue of the seed powder showed that the major
active constituent of the soluble dietary fiber is a galactomannan. Additional hypoglycemic
compounds were also present in other fractions. Aqueous extracts of TF leaves given orally
and intraperitoneally (i.p.) were also shown to produce a hypoglycemic effect in normoglycemic
and AL-DM rats. The oral and i.p. LD50 values were shown to be 9 and 1.9
g, respectively, and the main organ affected following i.p. administration was the liver.
No major target organ was affected following oral administration.59
Several mechanisms of action for TF’s hypoglycemic action were proposed. It appears
to take effect, at least in part, at the cellular level. In fact, TF antagonized the hyperglycemia
caused by alloxan or cadmium in rats. Cadmium has been shown to cause hyperglycemia
by increasing the release of epinephrine in intact rats and by decreasing the release of
insulin in isolated perfused rat pancreas.55 A higher level of antioxidants in animals on a
TF-supplemented diet as compared with animals on a control diet lead to the assumption
that TF seeds used as a supplement in the diet may normalize the disrupted free radical
metabolism.69 Another theory sprung from the fact that TF brought the high glucose-6-
phasphatase and fructose 1,6- phosphatase activities in the kidney and liver back to normal
levels in diabetic rats. These enzymes are involved in increased production of glucose and
fructose.70 TF powder supplementation also led to the normalization of creatinine kinase’s
activities in the diabetic rats and restored normoglycemia comparable with insulin and
vanadate (an antidiabetic agent).61 It was also shown that TF seed powder increased the
glycolysis and decreased the gluconeogenesis activities back to normal levels in the liver
and kidney in diabetic rats.62

7.7.3.1 Clinical Studies
Investigation on the hypoglycemic effect of whole TF seeds, extracted TF seed powder,
gum isolate from TF seed, cooked TF seed, and cooked TF leaves led to several findings.
Gum isolate significantly (p < 0.05) reduced BGL and increased insulin levels at 30- and
60-min intervals after administration. The dose was not given. The author repeated the
study in 5 diabetic patients given a daily dose of 25 g of defatted TF seeds for 21 days
with meals. At the end of the study, the glucose tolerance test showed significant hypoglycemic
activity. The dose, number of patients, patients’ ages and genders, and diagnostic
criteria were not mentioned. The author did conclude that TF was effective following
acute as well as chronic administration, its effect was not destroyed by cooking, and it
would be a good supplement to a diabetic diet.71
A significant hypoglycemic effect of TF was also reported in 10 type 1 diabetic patients
in a randomized trial. TF diet significantly (p < 0.05) reduced FBS and improved glucose
tolerance tests. It also produced 54% reduction in 24-h urinary glucose excretion, a significant
reduction (p < 0.05) in total cholesterol, and very low density cholesterol and triglycerides.
72
A crossover randomized trial66 with a diet enriched with TF seeds was performed on
two groups. The first group of 15 type 2 DM patients (ages 32 to 60; 33% females) was
randomized and given a TF-enriched diet during the first 10 days or during the second
10 days. The second group of 5 type 2 DM patients (ages 35 to 58) was randomized and
given a TF-enriched diet either the first 20 days or the second 20 days of the trial. The
authors of this study reported significant hypoglycemic activity (p < 0.05) in both groups.
However, the participant’s gender, demographic data, and data on the use of other
hypoglycemic agents were not mentioned.
Another randomized trial73 was performed on 10 type 2 DM patients (ages 38 to 54) in
which 2 groups (5 patients/group) were crossover between placebo and the TF-enriched
diet group. Patients were given 25 g of TF seeds incorporated in bread for 15 days. Authors
of this study reported significant (p < 0.05) hypoglycemic activity of TF and suggested
that the use of seeds in the treatment of DM merits further investigation.
A case control study74 investigated the hypoglycemic effect of TF in 60 type 2 diabetic
patients. Patients were kept on a restricted carbohydrate diet and given TF seeds 12.5 g
twice a day for 24 weeks. A significant reduction in glycosylated hemoglobin was noted.
The authors concluded that TF should be further investigated in the management of DM.
TF (9 g/day in 3 doses for 90 days) in 15 type 2 diabetic patients was found to produce
a significant (p < 0.05) hypoglycemic effect. It also produced a significant (p < 0.05)
reduction in serum cholesterol and triglycerides.75 It was also found to exert a hypoglycemic
effect in 20 healthy male volunteers (ages 20 to 30).65
The animal studies supported by the clinical experience indicate that TF has a significant
hypoglycemic activity and may prove useful in the management of DM. However, studies
using various biochemical parameters and endpoints should be carried out to determine
efficacy of TF as an adjunct to other hypoglycemic drugs.
7.7.4 Coccinia indica Wight (C. grandis, C. cordifolia Cogn)
Coccinia indica (CI), known as Bimbi or Kundura in India, is a climber with branched leaves.
CI is found wild in hedges and waste places in different parts of India. Fresh juice from
leaves, stem, and roots is used to treat diabetes, glycosuria, enlarged glands, and skin
diseases. The leaves and stem are also used as an antispasmodic and expectorant agent
in bronchitis.76

The hypoglycemic activity of CI has been reported in several animal studies.77,78 In fact,
the oral adminsitration of pectins isolated from CI produced a significant hypoglycemic
effect in normal rats.79 The ethanol extract in glucose-loaded normal rats showed similar
results.80 It was suggested that the hypoglycemic activity of CI is mediated through an
insulin secretagogue effect or through an influence on enzymes involved in glucose metabolism.
81 Also, it has been shown that powdered leaf suspension of CI produced a significant
hypoglycemic activity in AL-DM dogs but not in normal animals. In a glucose tolerance
test, however, the suspension did reduce the blood sugar levels.78,82 CI root extracts (water
or ethanol) have also been shown to have hypoglycemic activity in healthy rabbits.83–85
In a clinical double-blind controlled trial,86 a significant improvement (p < 0.05) in the
glucose tolerance was seen in 10 of 16 type 2 patients who received CI leaf preparation.
In another clinical study,87 500 mg/kg dried extract of CI given orally to 30 type 2 diabetic
patients for 6 weeks restored the enzymes involved in glucose metabolism back to normal
levels.
7.7.5 Pterocarpus marsupium (Papilionoidae)
Pterocarpus marsupium (PM), also known as pitsara, bijasal, pitasal, or red sandalwood in
India, is a moderate to large deciduous tree up to 30 m in height. Cold, aqueous extract
of the wood is used to treat diabetes. The paste of the leaves is used to treat abscesses
and skin diseases, and the extract of the bark is used as an astringent for gum and is also
useful in diarrhea.88
The hypoglycemic activity of PM has been reported in several studies.64,89–94 In fact, an
active constituent of PM, epicatechin, was reported to show the hypoglycemic effect in
AL-DM rats if given within 24 h after the administration of alloxan; no effect was seen if
given after 92 h.90 This indicates that epicatechin protected the pancreas from the direct
toxic effect of alloxan. Three phenolic constituents from PM were isolated and studied for
their hypoglycemic activity: marsupin, ptersupin, and pterostilbene. This hypoglycemic
effect in diabetic rats was comparable with that of 1,1-dimethylbiguinide.92
A significant decrease in BGL in normal rats (p < 0.001) 2 h after oral administration of
1 g/kg of aqueous extract of PM was evident in some studies. A significant decrease in
BGL in AL-DM rats after the oral dose of PM extract for 21 days was also reported.64
In one study,95 the antidiabetic effect of aqueous, ethanol, and hexane extracts of PM
bark in normal and diabetic rats was investigated. The ethanol extract at 0.25 g/kg oral
dose showed a more hypoglycemic activity than the aqueous and hexane extracts. The
same dose of ethanol extract was also more effective than glibenclamide, an oral hypoglycemic
agent.94 The ethanol extract of PM also exhibited a hypoglycemic effect in healthy
normal rats.95
These biological studies indicate that PM has substantial hypoglycemic activity and its
activity is not concentrated in any one constituent. The studies also show that these active
constituents are soluble in water, ethanol, and hexane.
7.7.5.1 Clinical Studies
The Indian Council of Medical Research (ICMR), Collaborating Centers, New Delhi,93
evaluated the efficacy of PM in newly diagnosed type 2 DM patients. Of 97 patients, 93
completed the daily dose of 2, 3, or 4 g of PM extract treatment for 12 weeks. The fasting
and postprandial BGLs in these patients fell significantly (p < 0.001) from the initial mean
of 151 and 216 mg/day, respectively. No significant change was noted in the mean plasma
lipid levels.

The above clinical studies coupled with the previously mentioned biological data provide
adequate scientific support for the use of PM in Ayurvedic management of DM.
7.7.6 Ficus bengalonsis L. (Moraceae)
Ficus bengalonsis (FB), also known as Vata, bor, bot, or Banyan tree, is a large evergreen tree
that sends down aerial roots for lateral growth. It is effective in deranged kapha and pitta.
Infusion of the bark is used to treat diabetes. The white milky juice of the plant is helpful
when applied on sores, ulcers, and cracked soles of the feet; it is also helpful for inflammation
and rheumatism. FB leaves contain quercetin-3-galactoside, rutin, and beta-sitosterol,
and its bark contains leucoanthocyanin and two flavonoids.96
FB has been shown to have hypoglycemic activity in several animal models. The results
of a comparative study of an ethanolic extract of FB bark, a glucoside isolated from the
bark, and tolbutamide in normal and AL-DM rabbits showed that the glucoside was more
active than the crude extract and half as potent as tolbutamide.97 Another study also
reported that a dimethoxy derivative of leucocyandin 3-O-beta-D-galactosyl cellobioside
isolated from the bark of FB decreased blood sugar levels very significantly on oral
administration in both normal and moderately diabetic rats. It also increased the serum
insulin significantly in the diabetic rats at a dose of 250 mg/kg for a 2-h period. In addition,
the oral dose of 100 mg/kg of the active principle given to diabetic rats for 1 month
produced a significant decrease in blood and urine sugar, certain lipid components in
serum and tissues, and glucose-6-phosphatase activity in liver. It further caused a significant
increase in body weight and the activities of hexokinase and human menopausal
gonadotropin coenzyme A (HMGCoA) reductase in tissues as compared with diabetic
control. The authors suggested that the mechanism of action of the principle may be related
to its protective and inhibitory action against the insulin-degradative processes.98
The extracts of FB bark also showed hypoglycemic activity in SZ-DM rats. In fact, the
oral dose caused an enhancement in serum insulin levels in normoglycemic and diabetic
rats. Each of these extracts stimulated insulin secretion when incubated in vitro with
isolated islets of Langerhans from normal as well as from diabetic animals. However,
the insulin secretion by beta cells was more apparent in the presence of pelargonidin
derivative than in the presence of another leucocyanidin derivative isolated from the
bark.99
Another study100 compared the antidiabetic effect of a dimethoxy derivative of perlargonidin
3-O-alpha-L rhamnoside isolated from FB bark with glibenclamide (2 mg/kg
and 0.5 mg/kg/day for a single dose and chronic dose, respectively). In moderately
diabetic rats, 250 mg/kg/day was used in the single-dose study and 100 mg/kg/day
of the extract in the chronic-dose study. Fasting blood glucose decreased by 19% and
improved glucose tolerance by 29% in the single-dose group. The corresponding effects
of glibenclamide were 25 and 66%, respectively, over the control values. In the 1-month
treatment group, the FBS levels decreased to almost half of the pretreatment levels in
both groups; glucose tolerance improved by 41% in the glibenclamide group and by
15% in the glycoside-treated group. Glycosurea was also decreased in both groups and
they appeared healthy.100
A glycoside of leucopelargonidin isolated from the bark of FB was compared with a
minimal dose of glibenclamide. Significant hypoglycemic, hypolipidemic, and serum insulin-
raising effects of the glycoside were demonstrated in moderately diabetic rats. The
effect was similar to that of glibenclamide. The main difference was that the former
significantly enhanced the fecal excretion of sterols and bile acids, whereas the latter had
no such action even though both controlled high blood cholesterol.101 A very similar isolate,

dimethoxy ether of leucopelargonidin-3-O-alpha-L-rhamnoside, given orally at 100 mg/
kg, produced significant hypoglycemic and serum insulin-raising effects in normal and
moderately AL-DM dogs during a 2-h period. The mechanism of action of the glycoside
compound seems to be similar to that of drugs that stimulate insulin secretion.
In a toxicity study,102 a single oral dose (0.2 to 1.8 g/kg) was given to mice. In a different
study, daily oral doses (100, 250, and 500 mg/kg) given to rats for a period of 1 month
did not show notable toxic effects. The compound was not lethal even at the high dose
of 1.8 g/kg in both species. A leucodelphinidin derivative isolated from the bark of FB
also showed hypoglycemic activity at a dose of 250 mg/kg in normal and AL-DM rats.
The effect was similar to that produced by glibenclamide (2 mg/kg) under the same
conditions. However, the plant product was less effective after a glucose load than
glibenclamide.103
7.8 Clinical Studies on Combination Formulas
7.8.1 Ayush-82
Ayush-82 is a mixture of four herbs: the seeds of Mangifera indica, Syzygium cuminii, and
Momordica charantia, and the leaves of Gymnema sylvestre. One hundred type 2 DM patients
(ages 40 to 70; 52% male) were given 5 g of Ayush-82 3 times a day for 6 weeks in
conjunction with Shuddha Shilajit.104 Shuddha shilajit is a mineral preparation of black
bitumen purified by triphala water. (Triphala is a mixture of Terminalia chebula, terminalia
bellerica, and Emblica officinalis.) Shilajit was given 500 mg twice a day for 2 weeks. Oral
hypoglycemic drugs were withdrawn after 2 weeks of treatment with Ayush-82. All
patients were advised to consume a a daily 1200-calorie diet. Although the average blood
sugar, FBS, and PPBS levels reduced significantly (p < 0.001) in some patients, the control
of diabetes was not good because 47% of the patients did not have their diabetes controlled
by the end of the study. The study had no comparison arm and the duration of the study
was too short.
The duration of treatment was extended to 24 weeks in another clinical trial on 350 type
2 DM patients, and all other parameters were kept the same as in the above study.105 On
the basis of a physician’s rating scale, the authors reported that 61% of the patients had
a good response, 12.9% had a fair response, and 25.9% had poor response. After the
treatment, FBS and PPBS levels were found to be significantly reduced (p < 0.001).105 It is
important to note that this clinical trial had no control arm and was not clear about the
time and method of withdrawal of the hypoglycemic agent. The results remain encouraging
and do support the concept that Ayurvedic formulas, because of their slow duration
of action, might yield better results if the treatment duration is extended.
7.8.2 MA-471
MA-471 is a mixture of the following herbs: Enicostemaa littorale, Phyllanthus niruri, Eugenia
jambolana, Melia azadirachta (indica), Terminalia arjuna, Aegle marmelos, and shilajit. This mixture
was found to produce a significant hypoglycemic activity and hypolipidemic activity
even in patients resistant to an oral hypoglycemic agent. This activity was demonstrated
while studying 69 type 2 DM patients, 6 of whom dropped out due to noncompliance and

3 of whom dropped out due to other illnesses. This study had three arms: (1) patients who
never had a hypoglycemic drug and DM was out of control despite dietary intervention
and exercise (n = 15), (2) patients who had DM under control through hypoglycemic agents
(n = 30), and (3) DM patients who did not respond to maximal dose of oral hypoglycemic
agents (n = 15). All patients ingested 500 mg tablets of MA-471 twice a day for an average
of 9 months. Arm 3 patients continued to take both M-471 and an oral hypoglycemic agent.
The authors observed a significant improvement in other clinical symptoms (e.g., polyurea,
fatigue, constipation, moderate improvement in weakness, polydipsia, giddiness, muscle
pain, palpitation, and anorexia). The authors deduced from the data that M-471 was beneficial
in all groups and that it can be used in conjunction with oral hypoglycemic agents.106
The results are encouraging and warrant further investigation.
7.8.3 Abraga Chendooram
Abraga chendooram (AC) is a mixture of abragum (purified black mica, 80 g), vengaram
(dehydrated borax, 0.5 g), and Saranaiver charu (juice of root of Trainthema decandra Linn.);
Adathodaielai charu (juice from the leaves of Adhatoda zeylanica Linn); and Alam Vizhuthu
Kudineer (root of Ficus benghalensis Linn).
Sixty type 2 DM patients (ages 21 to 70) who failed dietary control intervention and
showed no evidence of serious complications (e.g., ketoacidosis, nephropathy, neuropathy,
or retinopathy) were given 200 mg of AC in capsules twice daily for 45 days while their
caloric intake was restricted to 25 calories/kg of ideal body weight. The authors concluded
that the study demonstrated hypoglycemic effect and warrants further investigations. The
use of other hypoglycemic agents and the actual FBS levels were not shown in this trial.107
Another study also investigated AC in 130 type 2 DM patients (57% males). The patients
were given 200 mg of the drug in gelatin capsules twice daily for 45 days. The caloric
intake was restricted to 25 calories/kg body weight during the treatment. A significant
reduction (p < 0.005) in FBS and PPBS levels was observed. The authors reported that
57.9% of all patients gave a good response that was defined as FBS and PPBS lower than
normal accepted levels and absence of all clinical symptoms; the authors concluded that
the treatment could reduce blood sugar levels was combined with dietary controls.108
Major flaws in the design of this study included its short duration and the lack of defining
the use of other hypoglycemic agents. Although these results are encouraging, a longterm
study is still necessary to further substantiate the effect of AC.
7.8.4 D-400
D-400 is a mixture of Eugenia jambolana, Pterocarpus marsupium, Ficus glomerulata, Gymnema
sylvestre, Momordica charantia, Ocimum sanctum, and shilajit. This mixture investigated
D-400 in 38 diabetic patients (ages 35 to 76). The study had three arms: (1) patients
who did not respond to oral hypoglycemic agents (n = 19), (2) patients who did not
respond to diet and exercise therapy (n = 8), and (3) patients who were dependent on
insulin therapy (n = 6). All patients in all arms were given 2 tablets (weight not known)
of the drug 3 times a day for 6 months. The authors concluded that D-400 lowered the
blood sugar and cholesterol levels in the groups that failed the oral hypoglycemic
therapy and also in arm 2 but was less effective in arm 3 patients.109 The relative
proportion of each ingredient and method of preparation were not cited in the study.
Results are encouraging and warrant further investigation.

7.8.5 Sandan Podia
Sandana is a mixture of six parts of Tinospora cordifolia sugar and one part of each of the
following herbs: Santalum album (sandalwood) sawdust, Andropogon citratus (lemongrass)
root, Vitiveria zizanioides (vetiver) root, Syzygium aromaticum (clove) flower bud, Anacyclus
pyrethrum (pyrethrum) root, and purified Shilajit. The sugar is extracted from tinospora by
suspending the crushed plant in water overnight, decanting and drying the extract in the
sun, and resuspending the material in water overnight. The procedure is repeated three
times and the extract is dried and ground into a fine powder. The fine powders are mixed
thoroughly and put into 300-mg capsules, which were given to 20 type 2 DM patients
(ages 20 to 70) twice a day for 45 days. The FBS and PPBS of the patients decreased
significantly (p < 0.01) from 164.5 to 114.7 and 281.7 to 171.2 mg/day, respectively. Improvements
were also observed in other clinical symptoms, such as polyurea, excessive appetite,
weight gain, giddiness, polydipsia, indigestion, vomiting, and abdominal pain.110 Results
are encouraging and warrant a long-term study.
7.8.6 Kadal Azhinjil Choornam and Triphala Tablets
Kadal, a preparation containing roots and bark of Salacia chinensis, and triphala were given
to 25 type 2 DM patients. Kadal was given at 500 mg twice a day and triphala was given
at 2.5 g three times a day with water for 120 days.111 Authors reported a hypoglycemic
effect, but the results need to be confirmed.
7.8.7 M-93
M-93 is a mixture of four herbs: Aegle marmelos (bilva), Azadirachta indica (neem, nimba),
Ocimum sanctum (tulsai), and Piper longum (kalimircha). Thirty type 2 DM patients (ages 41
to 60) were treated with M-93, 1 g daily for 3 months.112 Patients with FBS >300 mg/day,
chronic renal failure, diabetic neuropathy, and diabetic ketoacidosis were excluded from
the study. The authors stated that M-93 showed a positive response after 30 days of therapy
and no adverse effect was observed.112 The results need to be confirmed.
7.9 Summary and Discussion
The review of literature indicates that the Ayurvedic concept of DM, including signs and
symptoms, etiology, and strategy of management, is not far from the current knowledge.
Herbs used in Ayurvedic therapies and the multi-herbal combination formulas have been
found to have a hypoglycemic effect in animal models of DM. Scientific studies done on
Considerable information was available about some of the herbs, namely, gymnema,
momordica, trigonella, coccinia, pterocarpus, and ficus, whereas other herbs have not been
studied as extensively. This makes Ayurveda a considerable choice as an antidiabetic
therapy that is safe, effective, and economic. The mechanism of antidiabetic action of these
herbs appears to be multifactorial: increased secretion or release of insulin, efficient use
of insulin, increased sensitivity of peripheral tissue to insulin, protective or regenerative
effect on pancreas, decreased synthesis, and increased breakdown of glucose. Because
these herbs have been used for thousands of years to manage DM patients, biological and
52 herbs (Table 7.6) and 7 multiherbal formulas have demonstrated hypoglycemic activity.

mechanistic studies confirming the hypoglycemic effect and clinical trials have not been
conducted as rigorously as would have been done for a new synthetic chemical with no
human experience.
7.9.1 Future Research Areas
7.9.1.1 Toxicity Studies
Although no serious adverse effects were reported in clinical trials and many of the herbs
are traditionally used as vegetables in regular diet, providing some degree of confidence,
the following toxicity studies should still be carried out at least on the most frequently
used herbs:
1. Single-dose toxicity study to determine LD50 dose
2. Subchronic toxicity study (120 days daily dose) in healthy animals and DM animal
models to determine the maximum tolerated dose and identify the target toxicity
organ
3. Lifetime feeding studies in normal and diabetic animals to determine long-term
beneficial effects (increase in survival time), possible protection of pancreas, or
toxic effects
7.9.1.2 Biochemical and Pharmacological Studies
There is a need for more biochemical and pharmacological studies. These studies will help
determine the optimum therapeutic dose and the major mechanism of the action of herbs,
giving the chance to maximize the efficacy by combining different mechanisms of action
at their optimum doses.
7.9.1.3 Clinical Studies
Clinical studies necessary to establish management of DM by Ayurvedic therapies are as
follows:
1. Definitive clinical studies with a rigorous protocol design; an optimum dose based
on toxicological data; Hb A1c, a good marker of DM control; and FBS and PPBS
levels
2. Possible relationship between the dosa predominance and response to Ayurvedic
treatments to validate the Ayurvedic concept of prognosis
3. Potential of Ayurvedic therapies to reduce or eliminate the use of synthetic oral
hypoglycemic agents
4. Possible resistance of DM patients to herbs or herbal formulas over a period of
time similar to oral hypoglycemic drugs
5. Ayurvedic management and use of herbs in high-risk population of type 2 DM
(family history of DM, lifestyle, and obesity) to determine if it can prevent or
reduce the incidence of DM
6. Combination of yoga and Ayurvedic therapies to identify any synergistic effects




Om Tat Sat
                                                        
(Continued...) 


(My humble salutations to H H Maharshi ji,  Brahmasri Sreeman Lakshmi Chandra Mishra ji and other eminent medical scholars and doctors   for the collection)

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