Evaluation of different parts of Berberis lyceum and their biological activities : a review

Berberis lycium is a common medicinal plant which belongs to family Berberidaceae. It is native to Pakistan and India. It is used medicinally for diarrhea, internal wounds, jaundice, internal colic, piles, diabetes, backache, rheumatism, throat pain, scabies, pustules, gingivitis, sub blindness, remittent fever and eye disorder. The various parts of Berberis lycium such as roots, stem, leaves, and fruit contain bioactive compounds like carbohydrates, proteins, fats, vitamin C, tannins, saponins, alkaloids, anthocyanins, berberine, berbamine, chinabine, baluchistanamine and sindamine. It contains various minerals i.e. sodium, phosphorus, copper, potassium, Iran, and zinc. The plant have shown many biological activities including anti-diabetic property, antimicrobial property, antihyperlipidemic property, hepatoprotective property, pesticidal property, antioxidant properties and wound healing properties. In light of current review there is a need of additional investigation and exploration regarding the medicinal value of this plant.


Introduction
Berberis lycium belongs to family Berberidaceae, [1] established this family as "Berberides" and is considered as one of the oldest angiosperms which possess a high number of discontinues genera [2].This family is comprised of 17 genera and 650 species.The English name of Berberis lycium is barberry [3], while "Kashmal" is the word used for the fruit of this plant [4,5], and roots are called as "Darhald" [6].The plant is a native species of Nepal [3], however, the species has been reported throughout Himalayas Mountains, temperate and semi-temperate localities of Afghanistan, Bangladesh, India, and Pakistan [7].In Pakistan grows in KPK, Baluchistan, Punjab and Azad Kashmir at an altitude of 900-2900 meters [8].Berberis lycium is a spiny deciduous shrub with an average height of 2-4 meters.The plant bear lanceolate leaves which are alternately arranged on the stem [9].The plant is self-fertile with hermaphrodite bright yellow colored flowers.The flowers are entomophilous, 11 to 16 in number and possess corymbs racemes inflorescence [10].March to July mark the flowering season of this species.The color of the flowers changes from yellow to purple on ripening (that is fruits).Berberis lycium produces an ovoid fruit which is up to 7 millimeter long and is known as Berries.The fruits start ripening from the 2nd week of May and remain to do so throughout June.Its fruit is usually used either cooked or raw and prepared into preservatives.The fruit is slightly acidic and juicy in nature.The plant possesses wide ecological amplitude and seeds can be grown in sandy, silty or loamy soils.The plant has a hard and branched root with a diameter ranging from 3 to 8 cm.The root bark is thick which is fissured externally and smooth internally [11] Studied root and fruit of B. lycium for mineral contents by using atomic absorption spectrophotometer.His findings revealed that the root contains 0.2% zinc (Zn) and 0.2% sulphur (S), while the sulphur (S) and zinc (Zn) contents in fruit were 0.1% and 0.8%, respectively.Similarly [23] examined roots and stem of B. lycium for lead (Pb), copper (Cu) and manganese (Mn) through atomic absorption spectrophotometer.According to their results, the quantity of Lead (Pb) found in stem and roots of the plant were 7.992 ± 0.106 and 4.360 ± 0.176 ppm, respectively.Result for Copper (Cu) quantity in stem and roots were 5.031 ± 0.176 and 4.360 ± 0.176 ppm, individually.Manganese (Mn) in the stem and root of the plant was 18.272 ± 0.212 and 15.500 ± 0.212 ppm correspondingly.In another study, Atomic absorption spectrophotometer was used by [10] to examine Phosphorous, Potassium, Iron, and Sodium, while by flame photometer Calcium quantity in the fruit of the said plant.The results showed the presence of Sodium (14.5± 0.11mg/100 g), Potassium (161.42 ± 0.41 mg/100 g), Calcium (18.272 ± 0.212 mg/100 g), Iron (2.61 ± 0.06 mg/100 g) and Phosphorus (38.0 ± 0.24 mg/100 g) in healthy amount.Leaves have also been reported to be plentiful in Iron (528.47 ± 0.02 μgg-1), Potassium (4077.00 ± 0.58 μgg-1), Mn (136.12 ± 0.01μgg-1), Phosphorous (1315.00 ± 0.01 μgg-1), Cu (53.41 ± 0.09 μgg-1), Zinc (37.71 ± 0.02 μgg-1), Sodium (79.00 ± 0.01 μgg-1) and Calcium (2389.00 ± 0.04 μgg-1).It was shown by [37] that Copper, Zinc, and Sodium were concentrated in root, Potassium in shoot, while Phosphorous, Mn and Calcium in leaves shown in (Table 1).
B. lycium is also screened for moisture, proteins, sugars, fibers, vitamin and dry matter.According to [19], roots of B. lycium possess moisture (20.5%), sugar (3.5%), dry matter (61.2%), fat (2.6%), protein (4.5%), Vitamin C (0.3%) and fiber (2.5%) in the given percentages.Fruits comprise moisture (12.5%),Vitamin C (0.8%), dry matter (62.5%), fat (1.8%), protein (2.5%), sugar (4.5%) and fiber (1.5%) in the given percentages.Roots showed the highest amount of fiber and fats while leaves showed highest amount of crude proteins [37] shown in (Table 2).Phytochemical screening of water extract of B. lycium by [22] showed the presence of Cardiac glycosides, Saponins, Hydrolysable Tannins, and Alkaloids.Analysis of fruit revealed the presence of tannins (8.9 ± 0.15 mg/100g), Phytic acid (2.5 ± 0.04 mg/100 g), β-Carotene (343.0 ± 0.89 μg/100 g), Phytate phosphorus (0.78 ± 0.06 mg/100 g), Hemicellulose (6.01 ± 0.41%), Anthocyanin (82.47 ± 0.29 mg/100 ml juice), Vitamin A (85.65 ± 0.17 μg/100 g) and Cellulose (7.94 ± 0.60%) [10].Essential alkaloids such as Berberine (Figure 1) and palmitine (Figure 1) in roots of B. lycium are found in a concentration of 4.5% and 3.1%, respectively, while in fruits   Results revealed lowered hyperglycemia at 50 and 100 mg/kg dose after 3 to 5 hours of treatment.The dose of 100 mg/kg showed the more pronounced effect on the subjects.Serum glucose level was decreased in oral glucose tolerance test in a dose-dependent manner by the plant extracts.Insulin-like effect was observed in hypoglycemia which could be due to peripheral glucose consumption.Behavioral changes and acute toxicity were not observed in the experimental animals at the given doses.A comparative study of pure berberine and ethanolic root extract of B. lycium was performed on alloxan induced diabetics rats and normal rats.Same doses of berberine (50 mg/kg) and ethanolic root extract were provided to the rats.Surprisingly, plant extract in comparison with berberine showed the same efficiency in reducing blood glucose level.An efficient effect was also seen on serum lipid profile, body weight and glycosylated hemoglobin [19] Shown in (Table 4).The fungal strain of Aspergillus terreus was also inhibited by the stem and root extract at MIC 0.62 and 0.31 μg/ml, respectively.Root extract also showed activity against Aspergillus flavus and Aspergillus spinulosus at MIC1.25 and 0.62μg/ml, respectively.B. lycium showed better immune performance against infectious bursal disease, newcastle disease, and infectious bronchitis.Coccidial oocysts/gram of feces showed a significant reduction in response to this plant [25].The plant was also mixed in containers of drinking water along with other medicinal plants to reduce pathogens and kill germs Shown in (  4).Antihyperlipidemic property B. lycium roots were used to study antihyperlipidemic property in male albino rabbits.From the results, it was concluded that oral use of crude powder (250 and 500 mg/kg) for four weeks significantly decreased triglyceride level, total cholesterol level and low-density lipids (LDLs) while high-density lipids (HDLs) were increased in rabbits.It was also observed that the weight of diabetic rabbits was highly stabilized by the provided doses [22].[27] Studied the hypolipidemic effect of root bark of B. lycium in broilers.Result showed significant decrease in the triglyceride, LDL, and total cholesterol while a dose dependent significant increase in HDL Shown in (Table 4).

Pesticidal property
Through Soxhlet apparatus, Petroleum ether and aqueous methanol extracts of B. lycium root were prepared and further dried under vacuum.Two higher doses (5000 and 10000 ppm) were used to study the activity of plant extract against pests.At the dose of 5000 ppm, the mortality rate shown by petroleum ether extracts were 25% against Helicoverpa armigera Hub and 92% against Aphis craccivora Koch.On the other hand at the dose of 10000ppm, the mortality rate was 26% against Tetranychus urticae Koch, 96%  4).

Wound healing property
Swiss Wister rats were used to study wound healing property of B. lycium` root extract.The models of wound repair used in the study were excision, incision and dead wound space while methanolic and aqueous extracts were used.Epithelialization and breaking strength of wounds were increased by both extracts.Collagen deposition, fibroblasts, and macrophages were found in aqueous treated rats.In methanolic treated rats, a significant amount of collagen deposition but with low fibroblast and macrophage was detected.Similarly, hydroxyproline content of granulation tissue and dry weight was also increased.In nutshell, it was concluded that methanolic extract was more efficient than the aqueous extract [30] Shown in (Table 4).

Antioxidant properties
Reactive oxygen species (ROS) such as hydrogen peroxide, -OH (hydroxyl radical) and superoxide anion are well known for their potential of causing diseases like Inflammation, Cancer, Rheumatoid arthritis, Aging and Atherosclerosis [56].However, the formation of ROS and related disorders in humans can be averted by Natural antioxidants [57].The root extract of B. lycium is known for antioxidant properties and strong reduction potential.Root extract converts potassium ferricyanide (Fe3+) to potassium ferrocyanide (Fe2+), which then reacts with ferric chloride and form a ferric ferrous complex that has an absorption maximum at 700 nm.This test is comparatively inexpensive and simple.Reducing power assay does not measure the 'Thiol group' comprising reagents [58] shown in (Table 4).

Conclusion
In the present review, various aspects of B. lycium have been discussed.B. lycium is a native species of Nepal but is also found throughout the Himalayas.It is a multipotential plant with many characteristics.The plant contains essential phytochemicals such as alkaloids, saponins, tannins, carbohydrates, phenols, glycosides, proteins and essential elements like zinc, copper, magnesium, potassium, sulfur, phosphorous, iron.Alkaloid berberine which has many pharmacological effects is also found in this plant.Berberine is anti-diarrheal but the exact mechanism of action is uncertain.Therefore, in vivo anti-diarrheal activities and in vitro spasmolytic activities of plant extracts are required to find the underlying mechanism.The plant extracts have been proved to possess pharmacological properties.The extracts are known to be antidiabetic, antimicrobial, antioxidants, pesticidal, antihyperlipidemic, hepatoprotective and wounded healers.However, the active constituents responsible for these pharmacological activities are unknown.Similarly, clinical data regarding the authenticity and efficiency of these pharmacological activities is very limited which pose a serious limitation to our knowledge and understanding.Thus more work is required to point out the underlying phytochemicals which are responsible for various activities of this plant.Also, a strong clinical data regarding these activities is also needed.
against A. craccivora Koch and 28% against H. armigera Hub and Plutella xylostella L.