TABLE 1.
Methodological characteristics, plant material and main results of included publications on anti-nociceptive and anti-inflammatory effects of B. pinnatum.
| Reference | Title | Type of study | Bryophyllum pinnatum material | Main outcome assessment | Main results |
|---|---|---|---|---|---|
| Pal and Nag Chaudhuri (1990) | Anti-inflammatory action of Bryophyllum pinnatum leaf extract | In vivo inflammation rodent models | Methanolic leaf extract | (A) Effect on carrageenan-induced paw edema | Results obtained at 300 mg/kg i.p. (A) 87.8% inhibition of paw edema |
| (B) Effect on peritoneal inflammation and capillary permeability induced by acetic acid | (B) inhibitory effect on peritoneal inflammation shown by reduction of total protein in exudate and inhibited capillary leakage | ||||
| (C) Effect on cotton pellet granuloma | (C) 38.7% inhibition of granulation tissue development | ||||
| (D) Effect in chronic arthritis models | (D) 83.3% reduction of inflammation in arthritis models | ||||
| Pal and Nag Chaudhuri (1991) | Studies on the anti-ulcer activity of a Bryophyllum pinnatum leaf extract in experimental animals | In vivo gastric lesion rodent models | Methanolic fraction of leaf extract | (A) Anti-ulcer activity on substance- and stress-induced gastric lesions | Results obtained at 100 and 300 mg/kg i.p. (A) Anti-ulcer activity in nine different experimental animals models |
| (B) Ulcer healing effect in acetic acid-induced gastric lesions | (B) Enhancement of the healing process in acetic acid-induced chronic gastric lesions | ||||
| Pal and Nag Chaudhuri (1992) | Further studies on the anti-inflammatory profile of the methanolic fraction of the fresh leaf extract of Bryophyllum pinnatum | In vivo inflammation rodent models | Methanolic leaf extract | (A) Effect on carrageenan-induced granuloma | Results obtained at 300 mg/kg (A) inhibition of granuloma development by 67.5% (s.c. application) |
| (B) Effect on picryl chloride induced ear edema | (B) Inhibition primary irritation (50% inhibition) and delayed hypersensitivity (i.p. application) | ||||
| (C) Effect on arachidonic acid-induced paw edema | (C) Inhibition of paw edema (i.p. application) | ||||
| (D) anti-oxidant effect on glucose oxidase-induced inflammation | (D) anti-oxidant effect by inhibition of release of oxygen containing radicals (i.p. application) | ||||
| Olajide et al. (1998) | Analgesic, anti-inflammatory and antipyretic effects of Bryophyllum pinnatum | In vivo inflammation and pain rodent models | Methanolic leaf extract | (A) Anti-inflammatory effect in carrageenan-induced paw edema | Results obtained after 50–200 mg/kg i.p. (A) Inhibition of paw edema (52%–66%) (B) Reduction of granuloma development (32% inhibition at 200 mg/kg/d) (C) Dose-dependent temperature reduction (D) Dose-dependent inhibition of writhing (11%–67%) |
| (B) Anti-inflammatory effect in cotton-pellet granuloma | |||||
| (C) Antipyretic activity in brewer’s yeast-induced pyrexia | |||||
| (D) Anti-nociceptive activity in acetic-acid induced writhing | |||||
| Pal et al. (1999) | Neuropsychopharmacological profile of the methanolic fraction of Bryophyllum pinnatum leaf extract | In vivo inflammation and pain rodent models | Methanolic leaf extract | (A) Analgesic effect in acetic acid-induced abdominal constriction model | Results obtained at 100 mg/kg i.p. (A) Reduction of writhing (25%) |
| (B) Analgesic effect in tail clip method | (B) No analgesic effect in the tail-clip model | ||||
| Igwe and Akunyili (2005) | Analgesic effects of aqueous extracts of the leaves of Bryophyllum pinnatum | In vivo inflammation and pain models in mice | Aqueous leaf extract | (A) Definition of LD50 | Results obtained at 300 mg/kg p.o. (A) No severe toxic effects (LD50 = 660.9 mg/kg body weight) |
| (B) Effect on pain threshold in hot plate method | (B) Dose-dependent increase of pain threshold by 193.5% | ||||
| (C) Effect on pain threshold in phenylbenzoquinone-induced writhing model | (C) Reduction of writhing by 80% | ||||
| Ojewole (2005) | Antinociceptive, anti-inflammatory and antidiabetic effects of Bryophyllum pinnatum (Crassulaceae) leaf aqueous extract | In vivo inflammation and pain rodent models | Aqueous leaf extract | (A) Anti-nociceptive effect in hot-plate and acetic acid model | (A) Dose-dependent anti-nociceptive effect at 25–800 mg/kg i.p (B) Inhibition of acute inflammation by 30% (90 min after treatment with 400 mg/kg p.o.) |
| (B) Anti-inflammatory effect in paw edema model | (C) Caused hypoglycemia in normoglycemic and diabetic rats at 25–800 mg/kg p.o | ||||
| (C) Antidiabetic effect in streptozotocin-induced diabetes mellitus model | |||||
| Gupta et al. (2010) | Anti-inflammatory activity of the leaf extracts/fractions of Bryophyllum pinnatum Saliv.Syn | In vivo inflammation model in rats | Various leaf extracts and fractions | Anti-inflammatory effect of extract and fractions on formaldehyde-induced paw edema model in rats | Inhibition of paw edema; methanolic extract was most effective leading to 64% inhibition at 500 mg/kg |
| Afzal et al. (2012) | Anti-inflammatory and analgesic potential of a novel steroidal derivative from Bryophyllum pinnatum | In vivo inflammation and pain rodent models | Aqueous leaf extract and isolated compound (urs stigmast-4, 20 (21), 23-trien-3-one) | (A) Carrageenan-induced paw edema model | (A) Extract led to reduction of paw edema by 87% (400 mg/kg p.o.) compound led to reduction of paw edema by 84% (300 mg/kg p.o.) |
| (B) Acetic acid induced writhing model | (B) Extract let to 80% protection against writhing (400 mg/kg i.p.) compound led to 75% protection against writhing (300 mg/kg, i.p.) | ||||
| Chaturvedi et al. (2012) | Pharmacognostical, phytochemical evaluation and antiinflammatory activity of stem of Kalanchoe pinnata Pers | In vivo inflammation rodent models | Stem extract not further characterized | (A) Acetic acid-induced vascular permeability | (A) Reduction of permeability (51% at 400 mg p.o.) |
| (B) Croton oil induced ear edema model | (B) Reduction of ear edema (63% inhibition at 400 mg applied topically) | ||||
| Coutinho et al. (2012) | Flowers from Kalanchoe pinnata are a rich source of T cell-suppressive flavonoids | In vitro T cell proliferation assay in lymphnode cells isolated from mice | Aqueous flower extract, isolated flavonoids | (A) Effect on T cell mitogenesis | (A) Flower extract more active in inhibiting murine T cell mitogenesis than leaf extract (IC50 = 37.5 μg/mL vs 84.9 μg/mL) |
| (B) Effect on cytokine production in lymph node cells | (B) All flavonoids inhibited murine T cell mitogenesis and IL-2 production, three out of five IL-4 production | ||||
| Cruz et al. (2012) | Kalanchoe pinnata inhibits mast cell activation and prevents allergic airway disease |
In vitro mast cell activation assay In vivo model of allergic airway disease in mice |
Aqueous leaf extract and flavonoids quercetin and quercitrin | (A) Effect on mast cell activation and cytokine production | (A) Extract (250, 500 or 1,000 μg/mL) and quercetin (25, 50 or 100 μg/mL) led to dose-dependent decrease of mast cell degranulation; quercetin reduced IL-6 and TNF concentrations |
| (B) Effect on OVA-induced airway hyperresponsiveness and airway inflammation | (B) treatment with extract (400 mg/kg) or quercetin (30 mg/kg) showed a reduction of airway reactivity; reduction in total cell count and especially in numbers of lymphocytes and eosinophils when treated with extract and quercetin; quercitrin had no effect | ||||
| Braz et al. (2013) | Antiulcerogenic activity of aqueous extract from Bryophyllum pinnatum (Lam.) Kurz | In vivo antiulcerogenic rat model | Aqueous leaf extract | Effect on indomethacin-induced gastric ulcers | Extract (1 and 2 g/kg) inhibited 45.5% of the indomethacin-induced ulcer index |
| Chibli et al. (2014) | Anti-inflammatory effects of Bryophyllum pinnatum (Lam.) Oken ethanol extract in acute and chronic cutaneous inflammation | In vivo acute and chronic mice ear edema models induced by different irritant agents | Ethanolic leaf extract | Topical anti-inflammatory effects on mice ear edema induced by different agents (A) Croton oil |
Extract (0.1, 0.5 and 1.0 mg/ear) inhibited ear edema induced by (A) Inhibition of 57% |
| (B) Arachidonic acid | (B) Inhibition of 67% | ||||
| (C) Phenol | (C) Inhibition of 80% | ||||
| (D) Capsaicin | (D) Inhibition of 72% | ||||
| (E) Ethyl phenylpropiolate | (E) Inhibition of 75% | ||||
| Ferreira et al. (2014) | Mechanisms underlying the antinociceptive, antiedematogenic, and anti-inflammatory activity of the main flavonoid from Kalanchoe pinnata | In vivo inflammation and pain mice model | Aqueous flowers extract (KPFE), ethyl acetate and butanol fraction, isolated flavonoid (KPFV) | (A) Effect on acetic acid-induced writhing | Results after s.c. application. (A) Inhibition of writhing (KPFE ID50 = 164.8 and KPFV 9.4 mg/kg) |
| (B) Effect on Croton oil -induced ear edema | (B) Inhibition of ear edema (KPFE ID50 = 4.3 and KPFV = 0.8 mg/kg) | ||||
| (C) Effect on TNF-α concentration | (C) KPFE and KPFV reduced TNF-α concentration | ||||
| (D) Effect on COX-1 and COX-2 activity | (D) KPFV inhibited COX-1 (IC50 = 22.1 g/mL) and COX-2 (IC50 > 50 g/mL) activity | ||||
| Tiwari (2015) | Comparative analysis of Bauhinia tomentosa L. and Kalanchoe pinnata Lam extracts with regard to their antinociceptive and antipyretic potentials in experimental animal models | In vivo inflammation and pain models in mice | Stem and root aqueous extract | (A) Anti-nociceptice effect in hot plate method | Results obtained at 200 and 400 mg/kg p.o. (A) Dose-dependent increase in latency time compared to control |
| (B) Anti-nociceptive effect in acetic acid-induced writhing model | (B) Stem extract inhibited writhing response | ||||
| (C) Antipyretic effect in yeast induced hyperthermia | (C) Root extract had antipyretic effects | ||||
| de Araújo et al. (2018) | Gastroprotective and antioxidant activity of Kalanchoe brasiliensis and Kalanchoe pinnata Leaf Juices against indomethacin and ethanol-induced gastric lesions in rats | In vivo acute gastric lesion rat models | Leaf press juice | (A) Effect in ethanol gastric lesion induction model | Results obtained at 250 mg/kg and 500 mg/kg p.o. (A) Dose dependent inhibition of up to 82% |
| (B) Effect in indomethacin gastric lesions induction model | (B) Dose dependent inhibition of up to 63% | ||||
| (C) Effect in inflammatory cytokines in gastric tissue | (C) Reduction in IL-1β, TNF-α and NFκB levels | ||||
| Indriyanti et al. (2018a) | Repairing effects of aqueous extract of Kalanchoe pinnata (lmk) pers. on lupus nephritis mice | In vivo lupus nephritis mice model/in silico identification of active compound | Aqueous leaf extract | (A) Effect on proteinuria | Results obtained at 200 mg/kg (A) Proteinuria level decreased to 30% in treatment groups |
| (B) Identify active compound binding to glucocorticoid receptor in silico | (B) Bryophyllin A is the most active compound in silico | ||||
| Indriyanti et al. (2018b) | T-cell activation controlling effects of ethyl acetate fraction of Kalanchoe pinnata (Lmk) pers on TMPD-treated lupus mice | In vivo lupus-like mice models | Ethyl acetate leaf fraction | Effect on leukocyte count | Total leukocytes reduced at 400 mg/kg |
| de Araújo et al. (2019) | Local anti-inflammatory activity: Topical formulation containing Kalanchoe brasiliensis and Kalanchoe pinnata leaf aqueous extract | In vivo paw and ear edema mice model | Aqueous leaf extract | (A) Local anti-inflammatory activity | (A) 5% extract showed statistically reduction of edema by 54% |
| (B) Effect on IL-1β, and TNF-α levels | (B) 2.5% and 5% extract suppressed IL-1β and TNF-α levels | ||||
| Naqvi et al. (2019) | Anti-platelet effect of Bryophyllum pinnatum aqueous extract in human blood | In vitro platelet aggregation assay | Aqueous leaf extract | Effect on platelet aggregation | Dose-independent anti-platelet effect on arachidonic acid and thrombin but not ADP |
| Pandurangan et al. (2019) | Evaluation of anti-inflammatory activity of Bryophyllum calycinum (Crassulaceae) on acute and chronic inflammation models | In vivo paw edema and granuloma mouse model | Whole plant ethanol/chloroform/n-hexane extracts | (A) Effect on Carrageenan-induced paw edema model | Results obtained at 400 mg/kg p.o. (A) Inhibition was observed for ethanol (92%), chloroform (88%) and n-hexane (86%) extracts |
| (B) Effect on cotton pellet induced granuloma | (B) Ethanol extract showed 57% inhibitory effect in granuloma model | ||||
| Andrade et al. (2020) | Anti-inflammatory and chemopreventive effects of Bryophyllum pinnatum (Lamarck) leaf extract in experimental colitis models in rodents | In vivo colitits rodent models | Hydroethanolic leaf extract | (A) Effect in 2.4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats and in dextran sulfate sodium (DSS)-induced colitis in mice | Results obtained at 250 mg/kg and 500 mg/kg (A) chemopreventive and anti-inflammatory effects and reduction in disease activity index score |
| (B) In vitro anti-inflammatory effects | (B) downregulation of toll-like receptor, IL-1β, TNF-α and NFκB | ||||
| Latif et al. (2020) | Phytochemical analysis and in vitro investigation of anti-inflammatory and xanthine oxidase inhibition potential of root extracts of Bryophyllum pinnatum | In vitro anti-inflammatory investigation | Aqueous and methanolic root extract | (A) Anti-inflammatory activity (protein denaturation) | (A) Aqueous extract had an IC50 value of 570 μg/mL |
| (B) Effect on xanthine oxidase inhibition | (B) Methanol extract most effective | ||||
| Lourenço et al. (2020) | Identification of a selective PDE4B inhibitor from Bryophyllum pinnatum by target fishing study and in vitro evaluation of quercetin 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside | In silico target fishing and In vitro enzyme inhibition assay | Single compound quercetin 3-O-a-L arabinopyranosyl-(1→2)-O-a-L-rhamnopyranoside | (A) Target fishing | (A) Anti-inflammatory activity explained by inhibition of PDE4B in silico |
| (B) Inhibition of PDE4B by compound | (B) In vitro experiments showed highly selective inhibition of PDE4B by compound (10 μM) | ||||
| Coutinho et al. (2021) | Wound healing cream formulated with Kalanchoe pinnata major flavonoid is as effective as the aqueous leaf extract cream in a rat model of excisional wound | In vivo excisional wound rat model | Aqueous leaf extract | Wound healing effect | Results obtained at 6% topical application |
| On day 12, wounds treated with extract cream showed 95% healing (compared to control 76% healing); better reepithelization and denser collagen fibers | |||||
| Dantara et al. (2021) | Effect of Bryophyllum pinnatum leaves ethanol extract in TNF-α and TGF-β as candidate therapy of SLE in pristane-induced sle balb/c mice model | In vivo lupus mice model | Ethanol leaf extract | Effect on inflammation markers in pristane-induced lupus mice | Results obtained at 10.5–42 mg/kg/d i.p |
| Percentages of maturation of B cells and TNF-α were decreased; percentages of TGF-β were increased (anti-inflammatory agent) | |||||
| de Araújo et al. (2021) | Gastric ulcer healing property of Bryophyllum pinnatum leaf Extract in chronic model in vivo and gastroprotective activity of its major flavonoid | In vivo gastric lesion rodent models | Aqueous leaf extract and isolated flavonoid (quercetin 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside) | (A) Ulcer healing properties of leaf extract in acetic-acid induced chronic ulcer model | (A) Treatment with the extract at 250 and 500 mg/kg stimulated the healing process (76% and 81% inhibition, respectively) |
| (B) Gastroprotective effects of isolated flavonoid in gastric lesions induced by ethanol and indomethacin models | (B) 5 mg/kg of isolated compound reduced ethanol-induced lesion by 49% and indomethacin-induced lesion by 51% | ||||
| (C) In vitro effect in acetic acid-induced chronic gastric ulcer model | (C) Downregulation of IL1-β, TNF-α, expression of COX-2 and NF-κB (p65) (250 and 500 mg/kg) | ||||
| Morais Fernandes et al. (2021) | Bryophyllum pinnatum markers: CPC isolation, simultaneous quantification by a validated UPLC-DAD method and biological evaluations | In vitro model on xanthine oxidase activity | Hydroethanolic leaf extract and isolated compounds | Effect on xanthine oxidase activity | Inhibitory effect on xanthine oxidase with IC50 values of >220 μg/mL (extract), 168 μM (kaempferol 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside), 124 μM (quercetin 3-O-α-L-rhamnopyranoside) |
| Santos et al. (2021) | Bryophyllum pinnatum compounds inhibit oxytocin-induced signaling pathways in human myometrial cells | In vitro assay on oxytocin induced activation of MAPKs in human myometrial cells | Leaf press juice and fractions | Effect on phosphorylation of MAPKs in human myometrial cells | Press juice (20 mg/mL) inhibited oxytocin-driven activation of MAPKS JNK/SAPK and ERK1/2 as did the bufadienolide-enriched fraction (2.2 μg/mL) by 50% |
| Singh et al. (2022) | Comparative evaluation of anti-arthritic activity of Pongamia pinnata, Bryophyllum pinnata and their combined formulation in FCA induced arthritis rat model | In vivo arthritis rat model | Ethanolic leaf extract | (A) Effect on arthritic score | (A) 500 mg/kg led to more than 40% reduction of arthritic score (B) 500 mg/kg led to 2.4 times longer pain response |
| (B) Anti-nociceptive activity in hot plate method | |||||
| de Araújo et al. (2023) | Gel formulated with Bryophyllum pinnatum leaf extract promotes skin wound healing in vivo by increasing VEGF expression: A novel potential active ingredient for pharmaceuticals | In vivo skin wound rat model | Aqueous leaf extract, topical gel 5% | (A) Wound healing effect on induced skin wound in rats | (A) Topical gel led to 60% reduction of wound area after 14 days compared to control |
| (B) Anti-inflammatory effect on wound tissue | (B) Reduction of IL1β and TNF-α | ||||
| (C) Effect on angiogenesis estimated by VEGF expression | (C) Increased expression of VEGF |