Phytotherapy and diabetes

Diabetes: Pathophysiology
One of the most prevalent metabolic illnesses, Type 2 Diabetes Mellitus (T2DM), is brought on
by a confluence of two main factors: improper insulin secretion by pancreatic beta-cells and
improper insulin response in insulin-sensitive organs. The molecular mechanisms involved in the
synthesis, release, and detection of insulin are carefully regulated activities because they are
necessary for maintaining glucose homeostasis. A metabolic imbalance that is the cause of the
disease's onset can result from flaws in any of the mechanisms involved in these processes. The
main features of T2DM are examined in this review, along with the molecular mechanisms and
pathways involved in insulin metabolism that result in T2DM and insulin resistance. To that end,
we compile the available information, paying particular attention to insulin synthesis, insulin
release, insulin sensing, and the subsequent consequences on several insulin-sensitive organs.
The paper also discusses the pathogenic elements that keep type 2 diabetes alive, such as diet,
exercise, gut dysbiosis, and metabolic memory. We also discuss some of the molecular pathways
that link T2DM and insulin resistance (IR), as well as cardiovascular risk as one of the most
significant consequences in T2DM, given that T2DM is linked to accelerated atherosclerosis
progression. [1]
We discover that there is still much to learn about the pathophysiology of diabetes mellitus.
Although it may seem like a cliché, this remark is accurate. The following article examines the
fundamental pathophysiology of both type 1 and type 2 diabetes mellitus as it is now understood.
It goes on to describe the "things that go wrong" when the body organs, particularly the brain,
have too much or too little glucose available to them. The article outlines the warning signs and
symptoms of acute diabetic ketoacidosis, hyperglycemic hyperosmolar nonketotic coma (or
condition), and severe hypoglycemia. When the person is in one of these acute stages, it finishes
with crucial considerations, and when the person is in a compromised state, it provides crucial
points regarding the control of diabetes. [2]

Citations
[1] (Galicia-García et al., 2020)
[2] (Pathophysiology of Diabetes Mellitus : Critical Care Nursing Quarterly, n.d.)
Diabetes Symptoms:
Diabetes is usually asymptomatic, however, there are some symptoms that commonly occur in both type
1 and type 2 DM as:

1. Polyphagia
2. Polyuria
3. Polydipsia
4. Hyperglycemia
5. Weight loss
6. Fatigue and weakness
 Symptoms may be mild or be shown gradually. 1

Diabetes Epidemiology:
Major risks for development of diabetes mellitus are:

1. Positive family history of diabetes

2. Age >35 years
3. Overweight (Body mass index ≥23 kg/m2) and obesity
4. (Body mass index ≥25 kg/m2)
5. Enlarged waist or upper body adiposity (>90 cm for men and >80 cm for women)
6. Presence of hypertension
7. Recent weight gain
8. Sedentary lifestyle
9. Gestational diabetes 2

Diabetes Screening Test:

Several tests exist to detect for the presence of DM such as:

1. Oral glucose tolerance test

2. Fasting blood sugar
3. Random blood sugar
4. HB1AC
5. Homa-IR “to detect insulin sensitivity” 3

1 Ramachandran A. Know the signs and symptoms of diabetes. Indian J Med Res. 2014 Nov;140(5):579-81. PMID:
25579136; PMCID: PMC4311308. 2 Ramachandran A. Know the signs and symptoms of diabetes. Indian J Med Res. 2014
Nov;140(5):579-81. PMID: 25579136; PMCID: PMC4311308. 3 Ramachandran A. Know the signs and symptoms of
diabetes. Indian J Med Res. 2014 Nov;140(5):579-81. PMID: 25579136; PMCID: PMC4311308.

Bulbus Allii Cepae

Scientific name and the part used: Bulbus Allii Cepae is the fresh or dried bulbs of Allium
cepa L. (Liliaceae) or its varieties and cultivars.

Pharmacological effect: Antihyperglycaemic activity of Bulbus Allii Cepae has been

demonstrated in clinical studies. Administration of an aqueous extract (100mg) decreased glucose-
induced hyperglycaemia in human adults. The juice of the drug (50mg) administered orally to diabetic
patients reduced blood glucose levels. Addition of raw onion to the diet of non-insulin-dependent diabetic
subjects decreased the dose of antidiabetic medication required to control the disease. However, an
aqueous extract of Bulbus Allii Cepae (200mg) was not active.
Dosage forms: Fresh juice and 5% and 50% ethanol extracts have been used in clinical studies. A
“soft” extract is marketed in France but is not recognized as a drug by French authorities. Dried Bulbus
Allii Cepae products should be stored in well-closed containers, protected from light, moisture, and
elevated temperature. Fresh bulbs and juice should be refrigerated (2–10°C).

Contraindications: Allergies to the plant. The level of safety of Bulbus Allii Cepae is reflected by
its worldwide use as a vegetable.

Interactions and other precautions: No general precautions have been reported, and no
precautions have been reported concerning drug interactions, drug and laboratory test interactions, WHO
monographs on selected medicinal plants 12 nursing mothers, paediatric use, or teratogenic or non-
teratogenic effects on pregnancy.

Example: Contractubex: antiscar remedy.

Radix Senegae
Scientific name and the part used: Radix Senegae consists of the dried roots and root crowns
of Polygala senega L., Polygala senega L. var. latifolia Torrey et Gray, or other closely related Polygala
species (Polygalaceae).

Pharmacological effect: Intraperitoneal administration of an n-butanol extract of the roots

(10mg/kg body weight) reduced blood glucose levels in healthy mice and in mice with streptozocin-
induced hyperglycaemia. Intragastric administration of a saponin fraction of a root extract reduced
glucose-induced hyperglycaemia in rats at a dose of 200mg/kg body weight (16). Intraperitoneal
administration of a saponin fraction of a root extract (25mg/kg body weight) significantly increased the
plasma levels of adrenocorticotropic hormone, cortisone and glucose in rats (P < 0.01). Intragastric
administration of a 100% methanol extract of the root decreased the absorption of ethanol in rats
(500mg/kg body weight).

Dosage forms: Chopped crude drug for decoctions and extracts. Store in a tightly closed container,
protected from light and humidity.
Contraindications: Pregnancy. Overdose with Radix Senegae preparations may cause nausea,
diarrhoea and vomiting due to gastrointestinal upset. In sensitive individuals, [Link] upset may
occur even at the therapeutic dosage

Interactions and other precautions: No general precautions have been reported, and no
precautions have been reported concerning drug interactions, drug and laboratory test interactions, WHO
monographs on selected medicinal plants 12 nursing mothers, paediatric use, or teratogenic or non-
teratogenic effects on pregnancy.

Example: A preparation of ammonium chloride, promethazine, senega extract, sodium benzoate,

squill tincture is present for respiratory tract infections.

Folium Azadirachti
Scientific name and the part used: Folium Azadirachti consists of the dried leaves of
Azadirachta indica A. Juss. (Meliaceae)

Pharmacological effect: A hypoglycaemic effect was observed in normal and alloxan-induced

diabetic rabbits after administration of 50.0 mg/kg bw of an ethanol extract of the leaves. The effect was
more pronounced in diabetic animals, and reduced blood glucose levels. The hypoglycaemic effect was
comparable to that of glibenclamide. Pretreatment with the extract 2 weeks prior to alloxan treatment
partially prevented the rise in blood glucose levels as compared with control diabetic animals. Intragastric
administration of 50.0–400.0 mg/kg bw of a 70% ethanol extract of the leaves significantly (P < 0.001)
reduced elevated blood glucose levels in normal and streptozocin-induced diabetic rats. A 70% ethanol
extract of the leaves signifi cantly (P < 0.05) blocked the inhibitory effect of serotonin on insulin
secretion mediated by glucose in isolated rat pancreas.

Dosage forms: Chopped crude drug for decoctions and extracts. Store in a tightly closed container,
protected from light and humidity.

Contraindications: Administration of Folium Azadirachti may reduce blood glucose levels and
should therefore be used with caution in insulin-dependent diabetic patients or patients taking oral
antihyperglycaemic drugs.

Interactions and other precautions: No general precautions have been reported, and no
precautions have been reported concerning drug interactions, drug and laboratory test interactions, WHO
monographs on selected medicinal plants 12 nursing mothers, paediatric use, or teratogenic or non-
teratogenic effects on pregnancy. Owing to potential genotoxic effects, the leaves should not be
administered during pregnancy or nursing, or to children under the age of 12 years.

Example: none.

Semen Trigonellae Foenugraeci

Part used
The dried ripe seeds
Antihyperglycaemic activity
Oral administration of 250.0 mg of an aqueous or methanol extract of seeds daily
to normal and diabetic rats significantly reduced blood glucose levels after eating
or the administration of glucose (P < 0.05). Intragastric administration of 250.0 mg
of an ethanol extract of the seeds daily for 28 days reduced blood glucose levels in
rats with streptozotocin induced diabetes, and increased the number of beta cells
and the diameter of pancreatic islet cells. Intragastric administration of 2.0 g/kg bw
or 8.0 g/kg bw of the seeds to rats with or without alloxan-induced diabetes
produced a significant decrease (P < 0.05) in blood glucose. Intragastric
administration of a single dose of 0.5 ml of a decoction or 200.0 mg/kg bw of an
ethanol extract of the seeds to mice with or without alloxan-induced diabetes
reduced serum glucose levels. Chronic administration of a high-fibre defatted
extract of the seeds in the diet (content not specified) to dogs with alloxan-induced
diabetes for 21 days decreased hyperglycaemia and glucosuria, and reduced the
high levels of plasma glucagon and somatostatin. Intragastric administration of an
acetone extract of the seeds (dose not specified) to fasted rats antagonized
hyperglycaemia induced by cadmium or alloxan but had no effect on normal
animals.
Adverse reactions
Allergic reactions to the seeds following ingestion or inhalation have been
reported. These reactions range from rhinorrhoea, wheezing, fainting and facial
angioedema. A 5-week-old infant had a 10-minute episode of unconsciousness
after drinking a tea prepared from the seeds; however, upon medical examination,
all tests were normal.
Contraindications
Semen Trigonellae Foenugraeci is contraindicated in cases of allergy to the plant
material. Owing to its stimulatory effects on the uterus, the seeds should not be
used during pregnancy.
Drug interactions
Owing to its effect on blood glucose levels in diabetic patients, Semen Trigonellae
Foenugraeci should only be used in conjunction with oral antihyperglycaemic
agents or insulin under the supervision of a health-care professional.
Carcinogenesis, mutagenesis, impairment of fertility
An aqueous and a chloroform/methanol extract of the seeds were not mutagenic in
the Salmonella/microsome assay using S. typhimurium strains TA98 and TA100.
The extracts were also not mutagenic in pig kidney cells or in trophoblastic
placental cells.
Other precautions
No information available on general precautions or on precautions concerning drug
and laboratory test interactions; teratogenic effects in pregnancy; nursing mothers;
or paediatric use.
Dosage forms
Dried seeds, extracts, fluid extracts and tinctures. Store in a tightly sealed container
away from heat and light.
Posology
(Unless otherwise indicated) Average daily dose. Internal use, cut or crushed seed,
6 g, or equivalent of preparations; infusion, 0.5 g of cut seed macerated in 150 ml
cold water for 3 hours, several cups; fluid extract 1:1 (g/ml), 6 ml; tincture 1:5
(g/ml), 30 ml; native extract 3–4:1 (w/w), 1.5–2 g. External use: bath additive, 50 g
of powdered seed mixed with 250 ml water, added to a hot bath; poultice, semi-
solid paste prepared from 50 g of powdered seed per litre of hot water, apply
locally.

Fructus Zizyphi
Part used
The dried ripe fruits
Antihyperglycaemic activity
Intragastric administration of a single dose of 1.0 g/kg bw of a 95% ethanol extract
of the dried seeds suspended in water lowered the mean blood glucose
concentrations in rabbits with alloxan-induced diabetes.
Adverse reactions
No information available.
Contraindications
No information available.
Warnings
No information available.
Precautions
Carcinogenesis, mutagenesis, impairment of fertility
An aqueous and a methanol extract of the fruits were not mutagenic in the
Salmonella/microsome assay using S. typhimurium strains TA98 and TA100 or the
Bacillus subtilis recombination assay at concentrations up to 100.0 mg/ml. A 70%
ethanol extract of the fruits, up to 4.0 mg/ml, was not mutagenic in either the SOS-
chromotest (Escherichia coli PQ37) or the SOS-umu test (Salmonella typhimurium
TA1535). Intragastric administration of 1.0 g of the fruits per day to rats for 15
months inhibited the growth of adenocarcinomas of the stomach induced by N-
methyl-N-nitro-N-nitrosoguanidine. Administration of a 95% ethanol extract of the
fruits in drinking-water, average daily dose 100 mg/kg bw, to mice for 3 months
had no significant spermatotoxic effects.
Other precautions
No information available on general precautions or on precautions concerning drug
interactions; drug and laboratory test interactions; teratogenic or non-teratogenic
effects in pregnancy; nursing mothers; or paediatric use.
Dosage forms
Dried fruits, aqueous and hydroalcoholic extracts. Store in a tightly sealed
container away from heat and light.
Posology
(Unless otherwise indicated) Daily dose: fruits 6–15 g
Citations
WHO monographs on selected medicinal plants vol. 3 (2007).

Pre and probiotics

Benefits have been shown with probiotics containing Lactobacillus acidophilus and
Lactobacillus casei Lactobacillus plantarum TN627 strain, Lactobacillus
plantarum, Lactobacillus gasseri BNR17, Lactobacillus reuteri and Lactobacillus
rhamnosus, but not with Lactobacillus bulgaricus. Other metabolic effects have
been reported with the use of probiotics in experimental studies on diabetes.
Bifidobacterium lactis was associated with low levels of lipids and insulinaemia, L.
casei CCFM0412 improved glucose tolerance, lowered lipid levels, enhanced
immune regulation and reduced oxidative stress; and Lactobacillus johnsonii led to
upregulated expression of proteins involved in intercellular tight junction assembly
and maintenance in the gut.

Bock PM, Telo GH, Ramalho R, Sbaraini M, Leivas G, Martins AF, Schaan BD.
The effect of probiotics, prebiotics or synbiotics on metabolic outcomes in
individuals with diabetes: a systematic review and meta-analysis. Diabetologia.
2021 Jan;64(1):26-41. doi: 10.1007/s00125-020-05295-1. Epub 2020 Oct 13.
PMID: 33047170.

Oleum Azadirachti
Scientific name and the part used: Oleum Azadirachti consists of the fi xed oil
obtained from dried seeds of Azadirachta indica A. Juss. (Meliaceae).

Pharmacological effect: Intragastric administration of 21.0 mg/kg body weight

(bw) of the oil re duced blood glucose levels in rats. A significant (P < 0.01)
reduction in blood glucose levels was observed in normal and alloxan-induced dia
betic rabbits after administration of 200.0 mg of the oil; the effect was more
pronounced in diabetic animals.

Dosage forms: Oil. Store in a tightly sealed container away from heat and light.
Contraindications: Administration of the oil may reduce blood glucose levels. It
should therefore be used with caution in insulin-dependent diabetic patients or
patients taking oral antihyperglycaemic drugs.
Interactions and other precautions: No information available on general
precautions or on precautions concerning drug and laboratory test interactions.
Posology (Unless otherwise indicated) Dose: 1.0–5.0 ml of oil for intravaginal
applications

Gummi Myrrha
Scientific anme and the part used: Gummi Myrrha consists of the air-dried oleo-
gum resin exudates from the stems and branches of Commiphora molmol Engler
(Burseraceae) and other related Commiphora species, including C. abyssinica
Engl., C. erythraea and C. schimperi Engl., but excluding C. mukul

Pharmacological effect: Intragastric administration of 10.0 ml/kg bw of a hot

aqueous extract of the resin per day for 7 days, reduced blood glucose levels in
diabetic rats. Intragastric administration of 150–175.0 mg/kg bw of two
furanosesquiterpenes isolated from the resin signifi cantly (P < 0.0036–0.0009)
reduced blood glucose levels in genetically altered obese diabetic mice, measured
27 hours after administration.

Dosage forms: Powdered resin, capsules, myrrh tincture, and other galenical
preparations for topical use. Store in a tightly sealed container away from heat and
light

Contraindications: Gummi Myrrha is used in traditional systems of medicine as

an emmenagogue, and its safety during pregnancy has not been established.
Therefore, in accordance with standard medical practice, Gummi Myrrha should
not be used during pregnancy

Interactions and other precautions: Topical application of a diluted (8%)

solution of an essential oil obtained from the resin was non-irritating, non-
sensitizing and non-phototoxic when applied to human skin. Application of an
unspecifi ed extract of the resin to human skin caused contact dermatitis. Use of
the undiluted tincture may give rise to a transient burning sensation and irritation
of the palate. Although no drug interactions have been reported, internal ingestion
of Gummi Myrrha may interfere with existing antidiabetic therapy owing to the
ability of the resin to reduce blood glucose levels. Patients taking anticoagulant
drugs or with a history of bleeding disorders should consult their health-care
provider prior to using the resin.
Posology (Unless otherwise indicated) Myrrh tincture (1:5 g/ml, 90% ethanol),
undiluted tincture applied to the affected area two or three times per day; mouth
rinse or gargle, 5–10 drops of the tincture in a glass of water; mouthwash or gargle
solution, 30–60 drops of the tincture in a glass of warm water; paint, undiluted
tincture applied to the affected areas on the gums or the mucous mem branes of the
mouth with a brush or cotton swab, two or three times per day; dental powder, 10%
powdered oleo-gum resin

Testa Plantaginis
Scientific anme and the part used: Testa Plantaginis consists of the epidermis
and collapsed adjacent layers removed from the seeds of Plantago ovata Forsk.
(Plantaginaceae

Pharmacological effect: Administration of the seed coats in the diet, 2.5%, for 18
weeks to mice with genetically-induced diabetes reduced blood glucose levels and
increased blood insulin concentrations.

Dosage forms: Dried seed coats available commercially as chewable tablets,

granules,
wafers and powder. Store in a well closed container, in a cool dry place,
protected from light.
Contraindications: Testa Plantaginis should not be used by patients with faecal
impaction, undiagnosed abdominal symptoms, abdominal pain, nausea or vomiting
unless advised by their health-care provider. Testa Plantaginis is also
contraindicated following any sudden change in bowel habits that persists for more
than 2 weeks, in rectal bleeding or failure to defecate following use of a laxative,
and in patients with constrictions of the gastrointestinal tract, potential or existing
intestinal blockage, megacolon, diabetes mellitus that is difficult to regulate, or
known hypersensitivity to the seed coats.

Interactions and other precautions: Sudden increases in dietary fi bre may cause
temporary gas and bloating. These side-effects may be reduced by a gradual
increase of fi bre intake, starting at one dose per day and gradually increasing to
three doses per day. Occasional fl atulence and bloating can be reduced by
decreasing the amount of the seed coats taken for a few days. Allergic reactions to
ingestion or inhalation of Plantago products have been reported, especially after
previous occupational exposure to these products. These reactions range from
urticarial rashes to anaphylactic reactions (rare). One rare case of fatal
bronchospasm has been reported in a Testa Plantaginis-sensitive patient with
asthma.

Testa Plantaginis should be taken with adequate volumes of fluid. Products should
never be taken orally in dried powder form owing to possibility of causing bowel
or oesophageal obstruction. In patients confined to bed or undertaking little
physical exercise, a medical examination may be necessary prior to treatment with
the seed coats
Posology: No information available.

Radix Rehmanniae
Scientific anme and the part used: Radix Rehmanniae consists of the dried roots
and rhizomes of Rehmannia glutinosa Libosch. or Rehmannia glutinosa Libosch.
var. purpurea Makino (Scrophulariaceae)
Pharmacological effect: Intragastric administration of an aqueous or methanol
extract of the roots, 200.0 mg/kg bw or 111.5 mg/kg bw, to rats decreased
streptozocin-induced hyperglycaemia. However, no such effects were observed in
diabetic rats treated orally with 1.6–2.0 g/kg bw of a hot aqueous extract or a
decoction of the roots daily for 8 days. These data suggest that the chemical
constituents responsible for the activity may be heat sensitive. Intraperitoneal
administration of 100.0 mg/kg bw of a polysaccharide-enriched extract of the roots
to mice decreased streptozocin-induced hyperglycaemia, reduced the activities of
glucose-6-phosphatase and phosphofructokinase, stimulated the activities of
glucose-6-phosphate dehydrogenase and hexokinase, and stimulated insulin release
from the pancreas.
Dosage forms: Dried roots and rhizomes for infusions and decoctions. Store in a
wellclosed container in a cool, dry place, protected from light
Contraindications: Radix Rehmanniae is contraindicated in chronic liver or
gastrointestinal diseases and in patients with diarrhoea. Owing to its potential
antiimplantation effects, the use of Radix Rehmanniae during pregnancy is also
contraindicated.
Interactions and other precautions: No information available on general
precautions or on precautions concerning drug and laboratory test interactions.
Posology (Unless otherwise indicated) Daily dose: 9–15 g of dried roots and
rhizomes as an infusion or decoction1

Folium Guavae
Scientific anme and the part used: Folium Guavae consists of the dried and/or
young leaves of Psidium guajava L. (Myrtaceae)
Pharmacological effect: Intragastric administration of a 50% ethanol extract of
the leaves to rats, at a dose of 200.0 mg/kg bw, prevented alloxan-induced
hyperglycaemia. A butanol fraction of the 50% ethanol extracts reduced alloxan-

1
WHO monographs on selected medicinalplants volumes 3 (1999-2009
induced hyperglycaemia in rats when administered at a dose of 25.0 mg/ kg bw by
gastric lavage. Intragastric administration of a 50% ethanol extract to rats at a dose
of 200.0 mg/kg bw did not stimulate insulin biosynthesis
Dosage forms: Crude drug, decoctions, extracts and teas.
Contraindications: Hypersensitivity or allergy to the plant material
Posology: (Unless otherwise indicated) Daily dose: 9–15 g of dried roots and
rhizomes as an infusion or decoction.

Radix Panacis Quinquefolii

Scientific anme and the part used: Radix Panacis Quinquefolii consists of the
dried roots of Panax quinquefolius L. (Araliacea)
Pharmacological effect: Intraperitoneal administration of an aqueous extract of
the root exhibited significant hypoglycaemic activity in mice with alloxan-induced
hyperglycaemia when administered at a dose of 10 g/kg body weight (bw) (p <
0.01). Activity-guided fractionation of the extract led to isolation of three glycans,
the quinquefolans A, B and C, which displayed significant hypoglycaemic activity
(p < 0.01, p < 0.05, p < 0.01, respectively) in normal mice and in mice with
alloxan-induced hyperglycaemia at a dose of 10, 100 and 10 mg/kg bw, of
quinquefolans A, B and C, respectively
Dosage forms: Crude drug, extracts, tinctures and capsules.
Contraindications: Radix Panacis Quinquefolii is contraindicated in cases of
known allergy or hypersensitivity to the plant material.
Posology: (Unless otherwise indicated) Oral dose: 3–9 g daily in divided doses2

2
WHO monographs on selected medicinal plants volume 4 (1999-2009)
 Pre and probiotics:
Bifidobacterium animalis subsp. lactis (BB-12) for 12 weeks and observed better
glycemic control and better HbA1c reduction. Similarly, Ismail et al. also
utilized B. animalis dn-173 010 for 16 weeks and saw favorable effects on lipid
profile, inflammatory markers, and glycemic management. Another selected study
by Toejing et al. also used single Lactobacillus paracasei HII01 strain for 12
weeks and suggested its possible use as an adjuvant therapy for T2DM. Sanborn et
al. used Lactobacillus rhamnosus GG for 12 weeks and reported alterations in
blood sugar regulation. Eight of the evaluated studies utilized a single probiotic
strain to treat T2DM, whereas the other 13 trials used several probiotic strains 3

3
Ayesha I E, Monson N R, Klair N, et al. (October 09, 2023) Probiotics and Their Role in the Management of Type 2
Diabetes Mellitus (Short-Term Versus Long-Term Effect): A Systematic Review and Meta-Analysis. Cureus 15(10):
e46741. doi:10.7759/cureus.46741