A Brief Review on Chemistry and Biological Activities of Bryophyllum pinatum (Lam.) Oken Family: Crassulaceae

Bryophyllum pinnatum (Lam.) Oken belongs to the family Crassulaceae, one of the important medicinal plants which has great significances to treat various disorders, ailments in human beings. This study tells phytochemical constituents and pharmacological activities of extracts of Bry.pin(Lam.) Oken. The aim of this review is to emphasise the recent and advanced research on different parts of plant extracts used. The forty secondary metabolites were isolated by different researchers where the most important includes flavonoids, terpenoids, glycosides, steroids and these secondary metabolites were responsible for various biological actions as antioxidant, anticancer, antidiabetic, anti-inflammatory, analgesics, wound healing and hepatoprotective actions which are incorporated. All this information gathered into this review were collected by using electronic search as PubMed, Research gate, Elsevier, Google scholar and Web science. Further studies also required on extracts for getting more information about mechanism of action, biological effects, safety, dosage required. By observing the medicinal uses and pharmacological profile of Bry.pin(Lam.) Oken might be transferred into a new various herbal formulation and can report for future.


INTRODUCTION
Our traditional medicinal system includes Ayurveda, Siddha and Unani. This Ayurveda concept emerged between 2500-500 BC in India 1 . The factual meaning of Ayurveda is "science of long life" and by using different modern approaches, techniques the herbal products derived or in combination from medicinal plants used for diagnose and treat the illness 2 . Mostly population of world depends on Traditional medicines (TM) for primary health care Now, the derived from herbal plants and herbal products has widely used 3 . The market would be increased which cost around $ five trillion in coming years by 2050 according to WHO. India is sitting on a gold mine of well-recorded and traditionally wellpracticed knowledge of herbal medicine with rich culture and natural biodiversity which offers a unique opportunity for drug discovery researchers .Man tried to explore and utilise these natural substances for prevention the illness and betterment for mankind. The levels of drug resistance are increasing and difficulties of being able to afford high cost in poor areas due to such problems today, Traditional medicines (TM) now became the roots of beneficial source of treatment. The use of ethno-botanical preparations for various reasons, is still continued by various cultures all around the world. They may be the oldest "evidence-based Medicine" 4 . Bry. pin (Lam.) Oken belongs to family of Crassulaceae which is a perennial herb commonly known as Paranbija, Patharchatta and Pashanbheda means stones dissolvers according to Ayurveda Fig. 1 5 . Bry. pin (Lam.) Oken is derived from Greek word Bryo means to sprout and phyllon means leaf and Pinnatum is the Latin adjective (adj.) word which has meaning "winged, pinnate" 6,7 . This plant is fleshy upright and succulent plant usually growing at about 60-120 cm tall. The drooping bell shaped flowers are greenish-yellow to pinkish-red in colour up to 7 cm long. The leaves are oppositely arranged with three or five leaflets and reproduction done by seeds or by leaf buds 8,9 . This family consisting 25 genus and around 425 species and the figure of plant is shown in Fig. 1 This plant can be known by various names as Cotyledon calycina, Cotyledon calyculata, Cotyledon calyculata, Cotyledon pinnata, Kalanchoe pinnata 11 and the vernacular name of this plant are Pashanabheda in Sanskrit, Air plant in English, Patharchatta in Hindi, Patharkuch in Bengali 6 . This miracle plant which is cultivated widely in America, China, India and Australia. It can be lined in to its popularity as house/garden plant due to its naturalisation of this plant and grows all over India in hot and moist areas, inhabiting warm and temperate climates from sea level to 8500ft and regarded as an invasive species. It is grown as a house ornament plant 11,10 . It is having folklore uses mainly as carminatives, haemostatic, astringent, wounds, boils, burns, menstrual pain, haemorrhage, scalds and diarrhoea and tonic . The leaves and leaf juice of the plant were used historically as antipyretic, antimicrobial, medicament, antitumor, inhibitor, antiulcer, medicament, astringent, antiseptic, antilithiatic and cough summarised in Table 2 12,13 . According to phytochemical studies the plants contained various secondary metabolites as steroids, alkaloid, flavonoids, phenols, tannins, bufadienolides and some acids which are responsible for various pharmacological actions mentioned in Table 1 12 and having high therapeutic value 10 . Various medicinal plants have their similar species by their genus so it will get difficult to understand their activity and their identity. Bry. pin (Lam.) Oken also similar to lavender scallops Bryophyllum fedtschenkoi and Bryophyllum delagoense, hybrid mother of millions of millions Bryophyllum x houghtonii, mother-of-thousands Bryophyllum daigremontianum. These species can be distinguished by macroscopic and microscopic characters as discussed below.

Botanical Description Macroscopic characters
The young roots are greenish brown in colour with tap root type of 7-10 cm long and light brownish colour of old roots. The powdered roots having sweetish taste and pleasant odour 14,15 . Leaves are simple, succulent, opposite, dark green in colour with 10-12 cm long and light green streaked in middle, pointed long petiole, asymmetric base, apex is obtuse. some leaves which are at upper side consisting 3-4 foliates with characteristic odour and bitter taste 15 . The leaf furnished buds on its structure which can give rise to a new plant. The stem is rough with lenticels in its skin with pleasant odour. Flowers are pale yellow in colour, streaking with redness, corolla 3-5 cm long cymes are paniculate, each flower produce on a stalk, 10-25 mm long. They have prominent, inflated, yellowish-green coloured sepals 25-55 mm long that are partially fused into a calyx tube. Seeds are numerous and obovoid. The fruits seeds are in brown colour having, 1mm long. Each fruit is covered with four carpels. The fruits are pappery and membranous with 15 mm long. The ovary has four carpels, slightly fused together in the center, with slender styles 16 .

Microscopic characters
The adaxial side is broadly shallow and convexed by abaxial side. It consists a thin adaxial epidermal layer and an abaxial layer both with less distinct cells which are circular and compact form and contained thick xylem band spreaded horizontally in a diffused way 14 25 . This miracle plant is also good source of carbohydrates, proteins, iodine and Sugar 6 contents too such as raffinose z1 , lactose z2 , sucrose z3 , glucose z4 , galactose, fructose and also various hydrocarbons like as alkanes having carbon C24-35, alkanols having carbon C27-34 11 . The aerial parts of this plant are rich in Macro elements 7 including calcium, potassium, magnesium, sodium, phosphorous and Microelements 8 including zinc, vitamins are tocopherol z5, ascorbic acid z7 , thiamine, riboflavin z6 , niacin z8 , pyridoxine z9 , glycine z10 , cysteine 6 . By the hydro-distillation of leaves of this Bry. pin (Lam.) Oken yielded essential oil which constituted nineteen compounds determined by GC/ MS contained oxygenated hydrocarbons, oxygenated monoterpenes, sesquiterpenes, oxygenated sesquiterpenes, curcumin, caryophyllene, octen-3ol. It also possessed bufadienolides as bryophyllin A, bryophyllin B and bryophyllin C which were also isolated from this Bry. pin (Lam.) Oken plant and reported it as insecticidal properties 23 . The leaves also contained chalcones, aurones, anthocyanidin.

Physicochemical properties
As literature surveyed, the physiochemical properties of Bry. pin (Lam.) Oken were observed in the following values 17 Total ash, Acid insoluble ash, Water soluble extractive value, Alcohol soluble extractive value were found to be as 5.1% 1.69%, water soluble ash 4.19%, 19.80%, 5.60% respectively 14,15 Chemical Constituents 18,19 This divine plant contains various active constituents which are responsible for pharmacological activities which are described below. The steroids as stigmasterols and bufadienolides were found or screened out from the shoots and dried leaves Bry. pin (Lam.) Oken by using dichloromethane (DCM) solvents and methanol for extraction respectively which all are shown as in Table 1. The extracts of leaves, roots, stem and  Ascorbic acid z7 , Niacin z8 , pyridoxine z9 , glycine z10 a-4-Hydroxy -3,5 -dimethoxy benzoic acid b-1,3,7-trimethylpurine-2,6-dione c-4-hydroxy-3-methoxy benzoic acid   Pharmacological Activity Antidiabetic Activity 6 Flavonoids and alkaloids were highly found when compared to steroids and terpenoids which were present in little while glycosides and reducing sugar were present moderately performed on rats. The ethanol extracts of T. africana leaves and Bry.pin (Lam.) Oken plants mixture with an equal amount and administered to albino rats to each three groups for 21 days. The different ratios of mixture of above plant extracts given to the groups and analysed their Plasma sugar contents, glycaemic status and serum lipid profiles of normal and streptozotocin-induced diabetic rats from the blood of tail vein at various 30, 60 and 120 min intervals which showed significant reduction (P 0.05) by STZ-induced diabetes glucose levels, density compound protein level and increase in high density compound protein level 26, 27 . The medicinal drug activity conjointly investigated of Bry. pin (Lam.) Lorenz Okenfuss plant's leaf liquid extract in rats, victimization contemporary egg albumin-induced pedal and streptozotocin STZ induced diabetes mellitus then this plant extract 25-800 mg/kg p.o. which also caused significant (P < 0.05-0.001) hypoglycaemia in rats. Thus, results of this animal study suggested Bry. pin (Lam.) Oken leaf aqueous extract possess micronutrient i.e. zinc which possessed hypoglycaemic activity 28 .

Hepatoprotective Activity
Liver is the important and largest organ in the vertebrates which detoxifies the toxins from body and helping in metabolism of body. By the chemicals and drugs used harmed the liver organ and its metabolism. Various medicinal plants used for treatment liver problems similarly, ethanolic extracts of Bry. pin (Lam.) Oken leaves also experimented on rats for liver cirrhosis, liver cancer and liver diseases. According to researchers, the aqueous and ethanolic extract of Bry. pin (Lam.) Oken in the doses of 250 and 500 mg/kg orally given to those rats which having injuries by induced N-diethyl nitrosamine which has showed a significant liver protection 10 . Other findings that the juice of the leaves of B. pinnatum and the ethanolic extract of the marc which was left behind after squeezing that juice also found hepatoprotective action against CCl 4 -induced liver disorder. It showed hepatoprotective action as observed In vitro and In vivo. The expressed juice was more found to be hepatoprotective than the ethanolic extract (EE) of Bry. pin (Lam.) Oken.

Antileishmanial Activity 6
Leishmania's is caused by parasite of leishmania type. It is spread by various type of sand-flies. The symptoms are skin ulcers, high fever and enlarged liver. This infection now became worldwide health problem majorly in developing countries. The incidence of the emergence of this disease has increased various health issues. So, there is an emergency requirement for effective drugs which can replace those current drugs in use 28 . According to phytochemical studies Some flavonoids like as quercetin and its rhamonsyl part which shows pharmacological activity. The quercetin, quercitrin, azelin were extracted from the plant showed antileishmanial activity 18 which acted their preventive action against amazonensis amastigotes by activation of nitrogen intermediates pathway-2 macrophages. The preventive effect of plant in leishmaniasis may not be due to a direct effect on the parasite itself but rather activation of the reactive nitrogen intermediates pathway of macrophages 30 .

Urolithiatic Activity
These are clumps of mineral that accumulate on inner lining of kidney. Symptoms are-dark colour urine, frequent urination, pain during urine, lower abdominal pain. According to Ayurveda this plant is also called stone dissolver. The extracts of leaf part of plant were exhibited to show the preventive effects on urolithiasis through dissolution of formed stones and through combating the formation of calcium oxalate crystals. There was decrease in body weight and increased in rest urinary parameters such as uric acid, creatinine, calcium, phosphorus and magnesium and in serum biochemical parameters also (creatinine, uric acid, urea, calcium, phosphorus and magnesium) due to induction of lithiatic on rat kidney by ethylene glycol in drinking water. Due to presence of flavonoids, phenolic compounds, saponins and steroids in the alcohol extracts of Bry. pin (Lam.) Oken which were responsible for urolithiasis activity 31 . When this alcohol extract (alc) treated with ethylene glycol (EG)-induced observed a sudden decrease serum biochemical and other urinary parameter and it decrease the urine volume, pH, magnesium and creatinine clearance, oxidative and histological damages. Some other researchers also reported In vitro inhibitory activity of the leaves of Bry. pin (Lam.) Oken plant on lithiatic 32 .

Anti-inflammatory and Analgesic Activity
Analgesics relieves pain by acting in CNS on peripheral pain mechanism without altering consciousness. Some steroids derivatives are also phytoconstituents of Bry. pin (Lam.) Oken which were isolated from leaves of the plant and to be active in red inflammation which showed percentage (%)inhibition 87.29 and 84.45 when compared with Diclofenac, standard drug towards carrageenan induced paw oedema model and acetic acid induced model respectively 33 . Similarly, it showed analgesic activity by acetic acid induced writhing test i.e. 75.72% in mice. So, the (% I) inhibition and (% P) protection against above mentioned models expressed their analgesic activity and anti-inflammatory of Bry. pin (Lam.) Oken due to the presence of steroidal compound. Some other research done where pain induced by chemically and thermally in experimental animals which were performed on rats to evaluate the analgesic activity against fresh egg albumin. The aqueous extract of Bry. pin (Lam.) Oken given to induced rats at 25-800 mg/kg showed protective effects 35 .

Immunomodulatory Activity
The aqueous extract of Bry. pin (Lam.) Oken as found to be inhibits mast cells activation and anaphylactic reaction and help in preventing allergic airway disease treated In vitro/vivo which gave a new light to immunomodulators functions 6 . There is another finding regarding immunomodulator activity where Lou M rats were used for experiment with parameters eosinophil count, cytokinin production, T-cell proliferation, histamine release assay were observed against anaphylactic shock 36,35 .

Antioxidant Activity
The leaf extract showed antioxidant action when it was performed on rats produced a concentration dependent increase in percentage antioxidant activity in DPPH radical scavenging activity. The optimum antioxidant activity of Bry. pin (Lam.) Oken extract was produced at 400 μg/mL concentration when compared with ascorbic acid and observe value of P<0.005 38 . The Bry. pin (Lam.) Oken extract produced increased antioxidant activity in ferric reducing antioxidant power compared with ascorbic acid (P<0.005) at 400μg/mL concentration 33 . The oxidative activity of Bry. pin (Lam.) Oken leaf extract was evaluated by DPPH and nitric oxide (NO) free radical scavenging models which showed 50% inhibition at 144.23 μg/mL concentration with aqueous extract and showed inhibition at concentration 117.42 μg/mL with alcoholic extract too. Similarly, other model of antioxidant Nitric oxide scavenging also showed 50% inhibition with both aqueous and alcoholic extract 34 .

Wound healing Activity
Wound healing is the process of healings the wounds and repairing the cuts and damaged skin layer by increasing the production of collagen and then epidermis tissues are regenerated. The stages for the process of wound healing inflammation, proliferation, remodelling. This activity shown by the water extract of Bry. pin (Lam.) Oken through the excision and incision model. This model gave a significant decrease in the epithelization period and scar area. The scar area was reduced with water extract up to (30.50 ± 0.84) treated group as compared to control group (43.66 ± 2.05) (p<0.001), So the result was production of collagen and granulation of tissues increased with the water extract of the leaf part when it was compared to control group of rats 39 . The three extracts of Bry. pin (Lam.) Oken leaf of petroleum ether (PE), water and alcohol were given to treated groups for evaluation wound healing action which showed increasing the breaking strength of incision wounds as compared to manage teams of rats within the dose of every four hundred mg/kg orally on healing of excision wound, re-sutured incision and dead area wound models in unusual person rats 10 . By investigation victimisation excision wound model in rats the ethanolic leaf extract expressed wound healing activity because of steroidal constituents.

Antibacterial Activity
Various medicinal plants were used for antibacterial activity. The different extracts of leaf (methanol, water, local solvents) got lyophilized and juice of Bry. pin (Lam.) Oken both have been shown its activity towards Gram-negative organisms like Escherichia coli ATCC 25922, Escherichia coli, bacteria Genus aeruginosa, Enterobacteria flexneri and Gram-positive organism like Staphylococcus aureus ATCC 25213, Enterococcus faecalis and a plant life by victimisation Agar well diffusion and broth dilution strategies to guage the minimum repressing concentration (MIC) and minimum germicidal concentration (MBC) at 512 mg/mL to 4 mg/mL concentration This activity turned against for skin infection and could formulated into skin soaps.

Anticancer Activity
The carcinoma was induced to specific group of experimental rats and these treated groups of animals were evaluated by given methanol (meth) and aqueous extracts (aq) of Bry. pin (Lam.) Oken with at doses of 100, 200 and 400 mg/kg body weight i.p. once a day for 7 days continuously after 24 h of cancer growth. The result was decreasing in tumour cell count and its weight (wt.) seen with the extracts treated group 41 . This result was dose dependent and showed antitumor activity towards Ehrlich ascites carcinoma due to the presence of bufadienolides 42,43 .

Neuropharmacological Activity
According to the studies the steroids (bufadienolides) and water-soluble constituents phytoconstituents present in this plant which were showing activity towards CNS depressants 44 . The sedation activity proposed by treated with 50-200 mg/kg aqueous leaf extract of Bry. pin (Lam.) Oken in treated mice which was found to be in decreasing exploratory/locomotor activity and gave a marked of sedative effects with a dose dependent way. The results of reduction pentobarbitone induced sleeping time and minimised the rate of strychnine and picrotoxin which induced seizures respectively. These studies showed the potential of Bry. pin (Lam.) Oken extracts to give neuropharmacological activity on the central nervous system 45,10 .

Side effects and toxicity
The leaf extract of this Bry.pin(Lam.) Oken plant contains not only flavonoids phenolic compounds, glycoside but this plant also possesses phenanthrene and bufadienolides which are toxic compounds and caused cardiac arrhythmia to the cattles after grazing Bry. pin (Lam.) Oken for 48 hours 46,47 .

CONCLUSION
Since the early days of humankind, the plants, herbs and botanical garden are used throughout the world for cure and prevention of disease. About 25% of drugs which are prescribed all over the world are derived from the plants. The previous literature and present studies of Bry. pin (Lam.) oken showed leaves and roots were consisting terpenoids, phenylpropanoids, flavonoids, steroids vitamins and some acids which would be a great help in new drug manufacturing for treatment of diseases. This plant grows majorly in the wild areas So, it is very important to conserve this medicinal plant which is known as miracle plant i.e. Bry. pin (Lam.) Oken and examined for their medicinal properties like antioxidant, anti-inflammatory, anticancer, urolithiatic and hepatoprotective property. In Odisha this plant known with the name of Basampatri are used in prevention to flatulence and in prevention of cough with ghee or garlic. People of Nigerians used filtrate of the leaves of plant in prevention of Asthma too. Though this plant showed some toxicity due to presence of bufadienolides which caused cardiac arrhythmia but only in cattles. So, it would be important to explore more of its species regarding their active constituents with their potential. Thus, we hope phytochemical studies and pharmacological properties helps and attracts the researchers in order to do new drug discovery and isolate, identify or characterise the structure of different active compounds which are responsible for activities. The pharmaceutical industries should adapt innovative step and necessary evidence for rational use of the plant as potent herbal medicine.