Therapeutic Insights into the Antidiabetic Activity of Selected Annona Species: A Comprehensive Review

Species

Taxonomy

Common Name

Leaf Characteristics

Flower Characteristics

Fruit Type

Native Place

Annona muricata [3,4]

Order: Magnoliales

Family: Annonaceae

Genus: Annona

Soursop, Munolla (India)

Large, oblong-ovate, dark green, 7.6-15.2 cm long and 2.5-7.6 wide.

Hermaphrodite, Solitary or cluster, yellowish-green, 3.2 to 3.8 cm in length

Ovate conical or heart-shaped fruit, spiny, 15- 35 cm long and 10-20 cm wide, Avg. 4kg weight

warmest tropical areas of the Americas, widespread across tropical and subtropical regions, including India, Malaysia, and Nigeria.

Annona squamosa [3,4]

Order: Magnoliales

Family: Annonaceae

Genus: Annona

Sugar apple, Sitaphal (India)

Simple, lanceolate, 5-17 cm long and 2-7 cm wide, light green.

Hermaphrodite, Solitary or cluster, greenish-yellow, fragrant, 2 to 2.5 cm in length

Round, heart shaped, ovate or conical, tuberculate surface, 5-10 cm long and 5-7.5 wide, 120-330 gm weight.

Caribbean and South American region, Central America, India, Indonesia, and southern Florida, West Indies.

Annona reticulata [3,4]

Order: Magnoliales

Family: Annonaceae

Genus: Annona

Custurd apple, Ramphal (India)

Oblong, lanceolate, membranous, green leaves, 16.7 to 24.3 cm long and 3 to 6 cm wide

Hermaphrodite, Drooping clusters, fragrant, slender, yellowish green, 1.5 to 3 cm in length,

Heart shaped, lopsided, irregular, or nearly round, or oblate, smooth or reticulated10-12cm long, 0.1 to 1 kg weight.

Caribbean and Central America, various tropical regions, including Southeast Asia and India.

Annona cherimola [3,4]

Order: Magnoliales

Family: Annonaceae

Genus: Annona

Cherimolia, Cherimoya, Lakshamanphal (India)

Ovate-lanceolate to elliptical, 10-25 cm long and 7.5 cm wide, velvety green.

Single, protogynous, fragrant flower, 2.5 to 3 cm in length

Heart-shaped, conical, oval, smooth or slightly bumpy, greenish yellow, 7.5 to 12.5 cm long, 200 to 700 gm weight

Subtropical highlands of western South America, specifically in countries like Bolivia, Colombia, Ecuador, and Peru

Species name

Chemical constituents

Annona muricata

[1, 4, 6, 7]

1)Acetogenins:

Seed:  Annomontacin, Annonacin A, cis-Annomontacin, Murisolin,

Muricin H, cis-Annonacin-10-one, Arianacin, Javoricin, Donhexocin, Murihexol, Cohibins, Gigantetrocin B, Longifolicin, Muricin A, B, C, D, E, F and G,

Annomuricatin B and C

Stem bark: Muricatin

Fruit: Epomuricenins-A and B, Epomurinins-A and B, Epomusenins-A and B, Muricin J, K and L

Fruit and Root: Sabadelin

Leaf: Annomutacin, Annopentocins, Annomuricine, Muricapentocin, Annomuricins A and B, Muricatocins A and B, Murihexocin A and B, Muricoreacin, Murihexocin C

Leaf and seed: Annonacin, Annocatacin, Annonacinone, Annocatalin, cis-Corossolone, Goniothalamicin, Isoannonacin, Corossolone.

Pericarp: Annonacin, Annonacin A, Annomuricin A

Root: Annonacin, Muridienins, Chatenaytrienins, Muricadienin,

Montecristin, cis-Panatellin, cis-Reticulatacin-10-one, cis-Uvariamicin IV, Coronin,

cis-reticulatacin, cis-Solamin, Cohibins

2)Alkaloids:

Fruits: Asimilobine, Nomuciferine, Annonaine

Leaf: dimethylcoclaurine, Anonaine, Annonamine, Norcorydine, Anonaine, Isolaureline, Xylopine

3)Flavonoids:

Leaf: Catechine, Epicatechine, Gallic acid, Chlorogenic acid, Kaempferol, Kaempferol-3-O-rutinoside, Quercetin-3-O-rutinoside, Quercetin-3-O-glucoside, Quercetin-3-O-neohispredoside, Quercetin-3-O-robinoside, Annoionols A and B, Annoionoside

Annona squamosa

[1, 4, 6, 7]

1)Acetogenins:

Bark: Bullatacin, Bullatacinone, Squamone

Seed: Neoannonin, Annosquamins, Annosquacin, Annosquamin, Annosquatin, Annotemoyin, Cherimolin, Diepomuricanin, Dieporeticenin, Dieposabadelin, Squadiolin, Squamostanin, Cyclosquamosin, Squamin A and B

2)Alkaloids:

Stem: ent-Kaur-16-en-19-oic acid, 16α,17-Dihydroxy-ent-kauran-19-al, 16α-Hydro-19-al-ent-kauran-17-oic acid, 16β,17-Dihydroxy-ent-kauran-19-oic acid, 16β-Hydroxy-17-acetoxy-ent-kauran-19-oic acid, 4α-Hydroxy-19-nor-ent-kauran-17-oic acid

3)Essential oils:

Leaf: Anonaine, Methylarmepavine, Caryophyllene, Cedrene, Caryophyllene, Germacrene D, Bicyclogermacrene, Quercetin-3-O-glucoside

Pulp fruit: α-Pinene, Limonene, Sabinene

Annona reticulata

[1, 4, 6, 7]

1)Acetogenins:

Leaf: Squamone, Annoreticuin-9-one, Annonaretin A

Stem bark: Reticullacinone, Rolliniastatin-2

Bark: Molvizarin, Bullatacin

Seed: Annoreticuin, Annoreticuin-9-one, Isoannonareticin, Rolliniastatin-1, 2, Annonareticin, 2, 4-cis-Isoannonareticin, Reticulacinone, Annoreticuin

2)Alkaloids:

Root: Neoannonin, Reticuline

Bark: Reticulatacin, Liriodenine, Coclaurine

Root bark: Anonaine, Michelalbine, Reticuline, Oxoushinsunine

3)Essential oils:

Leaf: Muurolene, Coclaurine, Copaene, Eudesmol

Root: Spathenelol, Copaene, Eudesmol, Muurolene

Bark: Patchoulane

Seed: Annoreticuin, Annoreticuin-9-one, Solamin, Annomonicin, Isoannonareticin, Rolliniastatin-1, 2 Squamone, Annonareticin, 2, 4-cis-Isoannonareticin, Solamin, Murisolin, Reticulacinone, Annomonicin, Sitosterol, Annoreticuin (ACT).

Fruit: Limonene, Pinene, Myrcene

Annona cherimola

[1, 4, 6, 7]

1)Acetogenins:

Seed: 2,4-cis-Annocherinones, Annocherin, 2, Isoannonacins, Annocherimolin, Annomolin, Annomocherin, Annomontacin, Annonacin, Asimicin,

2)Alkaloids:

Root: Corytenchine, Isocoreximine

Stem: Annocherine A and B, Artabonatine B, Romucosine H, Cherianoine

3)Essential oils:

Fruit: α-Pinene, α-Thujene, Terpinen-4-ol, Germacrene D

Annona species

Part and extract used

Inducer and animal strain used

Mechanism of action/ markers for study

Annona muricata

Leaves (100 mg/kg) and aqueous extract

55 mg/kg of streptozotocin i.v. and wistar rats

In STZ-diabetic rats, aqueous extract (100 & 200 mg/kg) decreased glucose by 75% and 58.22% over the course of one month. It also improved weight, lipid profile, antioxidant defence, and decreased food and water consumption. [8].

Annona liquid extract (100mg/kg)

(i.p) injection of STZ (40 mg/kg b.wt.) and wistar rat

Blood glucose, insulin levels, glycosylated hemoglobin (HbA1c), and the homeostatic model assessment for insulin resistance (HOMA-IR) were all improved by anona extract, which also decreased malondialdehyde (MDA) and restored liver antioxidant enzyme activity. [9].

Leaves and aqueous extract (100mg/kg)

-

According to a research, the leaves' aqueous gummy extracts were full of essential nutrients and bioactive substances that could have anti-hyperglycemic benefits in people with diabetes [10

Leaves and aqueous extracts

25 ml of glucose infusion through cannula inserted in intestine and wistar rat

Soursop leaf infusion reduced glucose absorption from 24.42?mg/dL to 18.24?mg/dL after treatment. [11].

Leaves (150mg/kg, 300 mg /kg, 600 mg /kg body weight) and Ethanol extract

40 mg /kg BW of alloxan by i.p injection and Swiss Webster mice

Soursop leaf ethanol extract (300 mg/kg) increased the size of the pancreatic islets in mice treated with alloxan from 16.83?±?3.55?µm to 32.29?±?4.14?µm. [12].

Annona muricata, Mangifera indica leaves and ethanolic extract Succinic acid and Hexamethylcyclotrisiloxane (1:1, 100 mg /kg b.w) same composition with dose 200 mg /kg.

Alloxan 140 mg /kg bodyweight and Wistar rats.

There are several ways to lower blood glucose levels, and treatments with the bioactive ingredients in mango and soursop leaves—succinic acid and hexamethylcyclotrisiloxane—seemed to improve glucose regulation by potentially enhancing the utilization of glucose in peripheral tissues [13].

Leaves (200mg/kg, 400 mg/kg) and Aqueous Extract

Alloxan Monohydrate I,p of 150mg /kg b.wt. and albino rat.

200 mg/kg was found to provide antihyperglycemic effects, increase body weight, enhance the blood lipid profile by lowering TCHO, TRIG, LDL, and VLDL, and raise HDL and the proportion of antiatherogenic index (AAI) [14].

Leaves (10mg/200gm, 20mg/200gm, 30 mg/200gm) and ethanolic extract

streptozotocin administered was 45 mg/200gm i.p and wistar rat.

The antihyperglycemic effects of A. muricata leaf ethanol extract are dose- related. The antihyperglycemic impact of 30 mg of soursop leaf ethanol extract is equivalent to that of 1.8 mg of acarbose [15].

Ripe fruit (750, 1000, 2000 mg/kg) and ethanolic extract

Streptozotocin (75 mg /kg I.p) and albino rat.

A high dose concentration of Annona muricata's ripened fruit ethanoic extract significantly reduced blood sugar levels. Ripe fruit pulp from A. muricata increases PCV, Hb, platelet counts, TWBC, neutrophils, eosinophils, basophils, monocytes, and lymphocytes proportionately [16].

Annona squamosa

Leaves (300 mg /kg) & Aqueous Extract

STZ (55 mg /kg body weight i.p) and albino wistar rat

Insulin-treated A. squamosa enhanced Hb, HbA1c, insulin levels, body weight, and adjusted lipid profile in diabetic rats while lowering blood glucose (264.4?±?8.5 to 98.1?±?5.9 mg/dL). [17].

Leaves (250mg/kg, 500 mg/kg) and aqueous extract

intraperitoneal injection of 65mg/kg streptozotocin and wistar rat

In diabetic rats, A. squamosa aqueous extract substantially decreased pancreatic TBARS and improved FPG, insulin, lipid profile, and liver glycogen (P?

Leaves (100mg/kg 400mg/kg) and hexane extract

STZ (50mg/kg, i.p) and CF strain

By lowering blood glucose by 41.18?±?2.46% (100 mg/kg) and 78.10?±?1.57% (400 mg/kg), the hexane leaf fraction had a hypoglycemic effect. Insulin levels increased to 11.58?±?1.80 and 16.26?µU/mL, respectively [19].

Leaves (350mg/kg) and aqueous extract

STZ (50mg /kg, i.p) -Wistar rats and Alloxan (i.v 80 mg /kg)- newzealand albino rabbit

FBG decreased in rabbits at 350 mg/kg from 373 ± 6.2 to 191 ± 5.4 mg/dL (48.7%), other than total hemoglobin increased by 10.8%.  FBG decreased from 246 ± 6.0 to 65 ± 10 mg/dL (75%), in diabetic rats.  Within two hours, serum insulin increased from 22.2±2.8 to 26.4±2.6 pmol/L (18.9%).[20].

Seed (200 mg/kg) and ethanolic and methanolic extract

I.P. injection of 150mg/kg of Alloxan monohydrate and wistar rat

In rats with alloxan-induced diabetes, crude methanol and ethanol extracts reduced blood glucose levels by 45.99% and 43.96% on day 7, respectively. [21].

Fruit pulp  (2.5, 5.0, 10.0 g /kg b.wt.)

alloxan (80 mg /kg b.wt.) ear vein of rabbit

Fruit pulp had no impact at 10 g/kg, but it decreased urine protein and sugar in diabetic rabbits by 70% (2.5 g/kg) and 80% (5.0 g/kg). [22].

Leaves (250mg/kg, 500 mg/kg) and alcoholic extract

intraperitoneal injection of 65mg/kg STZ 15 min after i.p administration of 110mg/kg of nicotinamide and wistar rat

Alcohol extract considerably improved lipid profile, liver glycogen, and pancreatic TBARS levels, however it had less of an impact on FBS in diabetic rats than standard medications (P?

Leaves (100 mg/kg) and ethanol extract

streptozotocin (50 mg/kg body weight i.p.) and Wistar rats

Within 30 days, A. squamosa leaf extract lowered Hb and HbA1c levels, raised insulin and C-peptide levels, and recovered blood glucose in diabetic rats.

Annona reticulata

Seed (50mg /kg and 100mg /kg) and ethanolic extract

STZ (i.p 55 mg /kg) and Wistar rat.

Extract from A. reticulata seeds (50–100 mg/kg)  raised islet area and insulin-positive cells, significantly decreased blood sugar, and enhanced insulin sensitivity, HbA1c, HOMA-IR, and glucose tolerance in diabetic rats. [25].

Bark and methanol (200 – 400 mg /kg), water (50 – 100 mg /kg)

STZ (i.p 55 mg/kg) and Wistar rat.

In SHSY5Y and DRG cells, methanol (200 & 400 mg/kg) and water extracts (50 & 100 mg/kg) demonstrated neuroprotection, decreased blood glucose, and enhanced pain thresholds in Randall-Selitto, hot plate, cold plate, and tail immersion tests.  Body weight did not change, and the effects were similar to those of insulin (5 IU/kg) and pregabalin (100 mg/kg). [26].

Leaves (250 mg/kg) and ethanolic, methanolic, aqueous, n-hexane extract

STZ (i.p 45 mg/kg) and Wistar rat.

Methanol extract improved the lipid profile by increasing HDL and decreasing LDL/VLDL, and it considerably decreased fasting blood glucose (up to 46.47%), which was comparable to glibenclamide (48.30%). [27].

Leaves (200mg/kg and 400mg/kg) and hydro-alcoholic extract

STZ (i.p 40 mg/kg) and Wistar rat.

A. reticulata hydroalcoholic extract (200 mg/kg and 400 mg/kg) decreased glucose by 54.73% and 47.80%, respectively, which is similar to the 55.25% impact of metformin in hyperglycemic rats. [28].

Leaves (100mg/kg) and hydro-alcoholic extract (chloroform, ethyl acetate, methanolic and residue fraction)

(i.p. 40 mg/kg) of STZ and wistar rat

In 14 days, the ethyl acetate fraction of A. reticulata leaves decreased FBG by 47.69%, which is comparable to the standard medication's 50.93% reduction, indicating strong glucose-lowering properties. [29].

Leaves (50mg/kg, 100mg/kg, 200 mg/kg, 400mg/kg) and methanolic extract

2 g glucose/kg and Swiss albino mice.

In mice given glucose, methanolic extract of A. reticulata leaves had dose-dependent antihyperglycemic actions, lowering glucose levels by as much as 56.1%. [30].

Stem bark and Petroleum ether, Chloroform, Ethyl acetate and ethanol (200mg/kg, 400mg/kg)

streptozotocin (STZ, 45 mg /kg; i.p.) and Wistar rat

Similar to glibenclamide, ethanolic extract of A. reticulata (200–400 mg/kg) reversed weight loss, excessive water consumption, and hyperglycemia in STZ-diabetic rats and dramatically decreased fasting glucose, perhaps via blocking hepatic glucogenosis and glycogenosis. [31].

Annona cherimola

Leaves (300 mg/kg), rutin(50mg/kg) and ethanolic extract

STZ 100 mg/kg intraperitoneally and BALB/c strain

When taken with oral antidiabetics, A. cherimola extract and 50 mg/kg rutin significantly reduced hyperglycemia, HbA1c, and lipid profiles. [32].

Leaves (300mg/kg) and tea infusion extract

STZ (100 mg/kg bw i.p.) and albino BALB/c mice

Annona cherimola leaf tea (300 mg/kg) reduced blood glucose, HbA1c, lipids, and stopped weight loss in diabetic mice when given once or repeatedly. [33].

Leaves (300mg/kg) and rutin (30mg/kg) separated with ethanolic extract

Alloxan monohydrate (i.v 125 mg/kg) albinos Sprague-Dawley rats,

Similar to acarbose (151.3 mg/dl), a single 300 mg/kg dosage of ethanol extract reduced glucose to 149.2 mg/dL, indicating that it functions as an α-glucosidase inhibitor. [34].

Leaves (300 mg/kg) and tea infusion extract

STZ (100 mg/kg bwt i.p.) and albino Balb/c mice

In diabetic mice, tea infusions from May to July significantly lowered blood glucose levels for up to seven hours; the August extract had the most impact. [35].

Leaves and ethanol, aqueous and dichloromethane (all 300 mg/kg)

Alloxan at (i.p. 74 mg/kg) BALB/c mice

In mice with diabetes induced by alloxan, ethanol extract (300 mg/kg) significantly reduced hyperglycemia at 2 and 4 hours. [36].

Leaves (100 mg/kg, 200 mg/kg) and ethanolic extract

alloxan monohydrate (i.p. 150 mg /kg b.wt.) and albino rats

Blood glucose was successfully lowered by Annona cherimola extract (100 mg/kg), particularly when used in conjunction with conventional therapy. [37].

Annona species

Part, extract and doses used

Assays performed

Mechanism of action/ markers of study

Annona squamosa

Leaves, extract (Aqueous, methanol) and (20-100μg/ml) 

Investigation of the inhibitory action of alpha amylase (1.0 g) in vitro

Both aqueous and methanol leaf extracts demonstrated dose-dependent inhibition of α-amylase; the methanol extract was more efficient than the aqueous extract (IC??: 47.78?±?2.45?µg/mL; IC??: 40.31?±?1.13?µg/mL). [38].

Fruit peel, extract (ethanol) and 10-100µg/ml

In-vitro Aapha amylase inhibitory assay

α-amylase was inhibited by an ethanolic extract of custard apple peel, with IC?? values ranging from 3.31 to 6.37?µg/mL.  The inhibition was higher in blanched samples (IC??: 3.31–5.53?µg/mL) than in fresh samples (6.37?µg/mL) and unblanched samples (4.92?µg/mL) [39].

Annona muricata

Leaves, extract (Aqueous) and 20µl

1)α-Amylase (20 μl, 2 U/ml) inhibitory activity

2) α-Glucosidase (20 μl,  1 U/ml) inhibition assay

Strong inhibition of α-amylase (IC???=0.90?μg/mL) and α-glucosidase (IC???=3.32?μg/mL) was demonstrated by silver nanoparticles, which substantially outperformed acarbose (IC???=10.20 and 610.65?μg/mL, respectively; P?< 0.0001).  α-glucosidase was found to be non-competitively inhibited by kinetic analysis. [40].

Peel, extract

(Aqueous) and 15–240 μg/ml, 10µl

1)α-amylase {500 μl of porcine pancreatic amylase (2 U m/L)} activity

2) α-glucosidase activity 200 mg of

bovine serum albumin

The aqueous extract was less efficient than acarbose (76.41%) at inhibiting α-glucosidase (71.56%) and α-amylase (60.46%).  By improving glucose absorption, increasing hexokinase activity, and decreasing β-cell apoptosis through PI3K/Akt gene upregulation, it decreased insulin resistance in diabetic rats.[41].  

pericarp, pulp, seed, extract (aqueous), 500 µL

1)α-amylase {0.5 mg/ml hog pancreatic α- amylase} inhibition assay

2)α-glucocsidase (1.0 U/ml) inhibition assay

The outcome demonstrated that each extract reduced ????amylase activity in a way that was dependent on concentration (00.8 mg/mL). However, as compared to acarbose (IC50 = 9.51 ± 0.11????g/mL), the pericarp extract (EC50 = 0.46 ± 0.03mg/mL) had the strongest inhibitory effect but the lowest, while the seed extract (EC50 = 0.76 ± 0.03mg/mL) had the least [42].

Leaves, extract (methanol), 250 μl  (1–5 mg/mL)

1)α-Glucosidase {500 μl   (1.0 U/mL)} (EC 3.2.1.20) activity inhibitory assay

2) 500 μl of porcine pancreatic amylase α-Amylase (EC 3.2.1.1) activity inhibitory assay (2 U/mL)

Methanol extract showed a substantial inhibitory effect on the carbohydrate-hydrolyzing activity of α-amylase. In comparison to acarbose, a well-known starch blocker, it shown a considerable (p < 0.05) inhibition against the carbohydrate-hydrolyzing activities of α-amylase (IC 50 = 112.27 mg/ml) and α-glucosidase (IC 50 = 34.85 mg/ml) [43].

Leaves, extract (methanol, hexane, ethyl acetate, n-butanol) and 250 μL (1-5 mg/mL)

1)α-Glucosidase (500 L of 1.0 U/mL) inhibitory activity assay

2) Assay for α-Amylase inhibition using 500 μL of pig pancreatic amylase (2 U/mL)

Both α-glucosidase (IC???=?71.06?±?1.45?mg/mL) and α-amylase (IC???=?73.88?±?1.58?mg/mL) were significantly, dose-dependently inhibited by the chloroform fraction of A. muricata (CFAm); both were significantly less effective than acarbose (IC?=?44.39?±?1.82 and 43.25?±?1.84?mg/mL, respectively; P?

Leaves, extract (methanol, ethylacetate, and n-butanol) and 100 µL of 0.5%

1) α-Amylase inhibition assay (100ul of 1.0 mg/mL)

Aqueous and hydromethanol extracts had the highest inhibitory efficacy, 48.84 ± 0.23% and 53.31 ± 0.33%, respectively, when the extracts' capacity to inhibit α-amylase was used to assess their antidiabetic activity. The compounds with the most affinity for the α-amylase active site include hepadecanolide, cyclotetracosane, and cyclopentadecanone 2-hydroxy- [45].

Leaves, extract (ethanol) and 250 μL

α-glucosidase (250 μL) assay

α-glucosidase inhibitory activity (IC50=0.17 ppm). Molecular weights of 638 amu at Rt=5.00 min, 612 amu at Rt=6.17 min, and 640 amu at Rt=7.51 min were recorded for one isolate of Annona muricata [46].

Leaves, extract (aqueous), MgO nanoparticles and 500μl

1) Inhibition of

alpha-amylase (0.5 mg/ml) enzyme

2) Inhibition of alpha glucosidases enzyme {1ml (1U/ml)}

A. muricata significantly inhibited the α-Amylase enzyme at different doses of 20, 40, 60, 80, and 100; the corresponding percentage inhibition was 32.59, 36.69, 39.16, 50.15, and 69.68, with an IC50 of 66.00μg/ml. it had a high percentage inhibition of 69.68±0.38 at 100μg/ml. At varying concentrations of MgO nanoparticles A. muricata (20, 40, 60, 80, and 100), the α-glucosidase enzyme was considerably inhibited; the % inhibition was 20.98, 23.41, 45.57, and 52.96. with a corresponding IC50 of 73.42μg/ml and 61.33. At 100 μg/ml, Annona muricata showed a high percentage inhibition of 61.33±0.742 [47].

Leaves, extract (aqueous) and 50µL

Alpha glucosidase (50 µL, 0.5 U/mL), inhibition assay

The AGI activity IC50 for each infusion was higher than that of acarbose.  Acarbose (1285 ± 148 μg/mL) had less α-glucosidase inhibitory effects than the guava, bay, and soursop infusions (0.083 ± 0.01; 0.025± 0.007; 0.533 ± 0.039 μg GAE/mL, respectively) [48].

Annona reticulata

Leaves, extract (methanol, aqueous,

 ethyl acetate and n-hexane) and (100, 200, 300, 400, 500 mg/ml)

1)Inhibition of alpha-amylase enzyme (500 mL) activity

2) suppression of the alpha glucosidase enzyme activity in yeast

At 200 mg/mL, α-amylase (IC???=?1051.58?±?7.17?mg/mL, 16.45%?±?3.42) and α-glucosidase (IC???=?713.09?±?2.37?mg/mL, 11.71%?±?2.12) were both dose-dependently inhibited by A. reticulata methanol leaf extract. [49].

Leaves, extract (aqueous, ethyl acetate, methanol, and n-hexane) and 100 to 500 μg/mL

Glucose

Uptake in Yeast (100 μL) Cell Model

In comparison to the other extracts, Methanol Extrat shown strong antidiabetic efficacy (48.55% at 500 µg/mL). A dose-related rise in the amount of glucose absorption was seen when the concentration of A. reticulata leaf extracts raised from 100 to 500 µg/mL. [50].

Annona cherimola

Peel, pulp and seeds (400ul)

1.0 mg mL−1of 2-naphthyl--D-glucopyranoside substrate

α-Glucosidase (4 ml, 5.0 U mL⁻¹)

bioassay

N-trans-p-coumaroyltyramine, N-trans-feruloyl tyramine, and N-trans-feruloylphenethylamine are the three α-glucosidase inhibitors found in A. cherimoya.  By lowering the enzyme concentration (10 to 5 U/mL) and incubation duration (60 to 10 min), HPTLC-bioassay was improved. [51].

Peel and leaves, extract (alkaloid methanol) and 50 µL

α-glucosidase (25 µL, 1 U mL^-1) inhibition assay

With activity 7.3 times lower than acarbose, cherimoya leaf extracts demonstrated substantial α-glucosidase inhibition; peel extracts had the lowest IC?? (1798.12?±?85.28?µg/mL).  This effect might be exacerbated by strong AGIs such as N-trans-feruloyl tyramine and N-trans-p-coumaroyltyramine. [52].   

Fruit pulp, extract (hydro-alcoholic) and 7.5 and 15 g/mL

Alpha glucosidase {(0.5 unit/mL) from Saccharomyces cerevisiae yeast} Activity Assay

Annona cherimola pulp extract substantially suppressed albumin glycation and α-glucosidase activity (Ki?=?17.72?μg/mL), with 7.5?g/mL and 15?g/mL inhibiting 50% and greater of advanced glycation end-products (aAGE) generation in vitro.