Bacopa Monnieri 추출물 분말에는 어떤 활성 성분이 있나요?

학명:Bacopa monnieri (L다다.)Wettst. 흰꽃돼지풀 (white-flowered pigweed)은 인도의 아유르베다, 중국 전통의학에서 쓰이는 약용식물이다.열대 및 아열대 지역에 널리 분포하는 scrophulariae 과에 속하는 서서히 자라고 살이 많은 다년생 초본이다.전통적으로 기관지염, 천식, 이질 및 다양한 염증성 질환을 치료하기 위해 사용됨;인도에서는 신경계 강장제로 유명하며, 현대 약리학 연구를 통해 효능이 확인되었다.임상적으로는 기억력 강화, 간질 치료, 불면증 완화 등에 사용되며 가벼운 진정제로도 쓰인다.연구 분석 결과, Scutellaria baicalensis saponins (hersaponin), Scutellaria baicalensis saponins (bacoside, white flower pigweed saponin) A 및 B, apigenin-7-glucuronic acid glycoside, luteolin-7-glucuronic acid glycoside 등 추출분말의 활성 성분을 확인하였다.

1 활성 성분

Bacopa monnieri (Bm)의 신경영양성 및 항당뇨 활성은 알코올 추출물의 글리코사이드 분획에 집중되어 있으며, 혼합물로서 추출물에 존재하는 글리코사이드 성분의 함량이 높다.1993년부터 메탄올 또는 에탄올을 이용하여 얻어진 Bm 추출물의 당분 분획에 대한 종합적인 화학적 연구가 수행되어 주로 수많은 새로운 당분 화합물을 분리, 확인하였다트리테르페노이드 사포닌과 펜에틸글리코사이드.

트리테르페노이드 사포닌 1.1

Chakravarty[1-3]는 인도 콜카타 교외에서 채집한 Bm 으로부터 5개의 새로운 트리테르페노이드 사포닌, bacopa-sides I-V를 분리하였다.이 중 2개는 jujubogenin glycoside 이고, 3개는 pseudo-jujubogenin이다glycosides.

Bm의 식물 전체를 석유 에테르와 메탄올로 추출하였다.메탄올 추출물 (ME)을 실리카겔 크로마토그래피로 분리하여 bacopaside I (1)을 얻었다.저극성 분획을 실리카 겔 크로마토그래피와 preparative HPLC로 더욱 분리하여 bacopaside II (2)를 얻었다.ME는 물과 n-butanol에 분포하였고, n-butanol 분획은 실리카겔에 흡수되었다.추출과 CHCl ₃, EtOAc,나 ₂ CO, 그리고 CHCl ₃-MeOH 순서 대로다.이 날 ₂ CO 받았을 추출 하여실리 카겔 크로마토그래피와 예비 HPLC, bacopaside III, IV 및 V (3-5)를 산출한다.

이러한 화합물의 구조는 주로 화학 및 2D NMR 분광법에 의해 설명되었다.1은 화합물 3-O-α-L-furanarabinosyl (1) → 2)-[6-O-sulfonyl-β-D-pyranoglucosyl (1 → 3)]-α-L-pyranarabinosyl pseudo-jujuboside, 복합 2는 3-O-α-L-furanarabinosyl (1) → 2)-[β-D-pyranoglucosyl (1 → 3)-β-D-pyranoglucosyl pseudo-jujuboside;3은 화합물 3-O-α-L-furan arabopyranosyl (1) → 2)-β-D-pyranoglucopyranosyl 산성 jujuboside, 복합 4는 3-O-β-D-pyranoglucosyl (1 → 3)-α-L-pyranarabinosyl 산성 jujuboside, 복합 5가 3-O-β-D-pyranoglucopyranosyl (1 → 3)-α-L-pyranoarabinosyl pseudo-jujuboside다.

호우 [4] 등은 중국 타이난에서 Bm의 신선한 식물 전체를 채집했다.메탄올 추출물의 부탄 수용성 분획은 실리카 겔과 다공성 고분자 겔에 반복적으로 컬럼 크로마토그래피를 가하여 5개를 산출하였다새로운 글리코사이드 화합물다.두의이 러한 pseudo-sapindoside로 확인 되었고 sapindoside 반면 다른 두 화합물, bacopaside III, 구조를 가지 3-O-[6-O-sulfonyl-β-D-pyranoglucosyl (1 → 3)]-α-L-pyranarabinosyl pseudo-sapindoside aglycone (화합물 같은 화합물로 연결 되지 않은 6, 3);bacopasaponin 구조를 G는 3-O-[α-L-furanarabinosyl (1) → 2)]-α-L-pyranarabinosyl 산 대추 glycoside aglycone (7).

이후 가라이 등 [5-7]은 6개의 담마라네형을 분리하였다triterpenoid saponinsBm 메탄올 추출물의 n-butanol-soluble fraction에서 bacopasaponin A-F (8-13)로 명명하였다.이 러한 가운데, 12살과 13 화합물은 bioactive aconitane-type 이중 탄소 체인에 saponins, 구조와 3-O-[β-D-pyranoglucosyl (1 → 3) {α-L-furanarabosyl (1 → 2)}-α-L-pyranarabosyl-20-O-(α-L-pyranarabosyl) saponogenin 및 3-O-[β-D-pyranoglucopyranosyl (1 → 3) {α-L-furanarabinosyl (1 → 2)}-β-D-pyranoglucopyranosyl]-20-O-α-L-pyranarabinosyl 산 jujuboside다.

자인 등 (8-10)은 건조 Bm 전분 식물의 에탄올 추출물에서 아세트-가용성 분획을 추출하여 pseudo-purslane을 분리하였다사포닌 A와 B얻고, 원유 pseudo-purslane 사포 닌 ₁ (14)에 의해 반복 되는 실리 카 겔 열 크로마토그래피 chloroform-methanol 그라 데이션 용출 가 그 뒤를이었다.  

에틸 아세테이트 불용성 분획을 재결정화하여 순수한 화합물 14를 수득 하였다.에탄올을 받았을 추출 하여 반복적으로 실리 카 겔 열 크로마토그래피에 틸을 가 진 녹아서 분리 됩 acetate-increasing acetone-water 그라 데이션 용매 (90:10) 시스템, 굴복을 포함하는 일부 pseudo-purslane 사포 닌을 ₂ (15)이다.성충이 반복 되는 역 C 한 조사를 받았₁ ₈ 열 크로마토그래피과 녹아서 분리 됩 acetonitrile-water (30:70) 순수 한 복합 15를 얻을 수 있다;아세톤수 (40:10)의 구배로 물 포화 에틸 아세테이트로 용출하여 가짜 퍼슬레인이 풍부한 분획을 산출하였다사포 닌을 ₃(16), 뒤이어 신속 한 열에 크로마토그래피 Bondapak C ₈ 열과 elute acetonitrile-water (30:70), 구매 순수 한 16 화합물이다.화합물다의 구조는 3-O-[α-L-furan arabitol (1 → 3)-α-L-pyran arabitol] 산성 jujuboside, 3-β-[O-α-L-furan arabitol (1 → 6) 가 될-  [α-L-pyran arabosyl (1 → 5)] 가 될-α-D-furan glucosyl) oxo] pseudo-jujuboside과 3-β-[O-β d-pyran glucosyl (1 → 3) 가 될-[α-L- furan arabosyl (1) → 2)] 가 될-β-D-pyranoglucosyl) 옥시] 산 대추 glycoside다.Pseudopueraria saponin A₃는 saponin 혼합물의 주성분이자 활성성분이다.

펜에틸알코올 글리코사이드 1.2

Chakravarty 등은 Bm 전분 식물의 메탄올 추출물을 에틸아세테이트로 추출하여 실리카겔 컬럼 크로마토그래피를 수행하고, CHCl₃-MeOH (9:1, 8:2)로 용출하여 17, 18 화합물을 포함하는 젤과 같은 물질인 fraction A를 얻었으며, 추가로 CHCl₃-MeOH (7:3, 6:4)로 용출하여 19, 20 화합물을 포함하는 혼합물인 fraction B를 산출하였다.위의 분수 열 크로마토그래피 된 작업에 의해 분리 되었Diaion HP-20 열로 녹아서 분리 됩 MeOH-H ₂ O (1:1 및 1:3), 그리고 그에 의해 정화 잔류 preparative HPLC (H ₂ O-MeCN, 9:1 모 바 일 단계로), 양보 순수 한 화합물을 17대,이 모든 것은 phenethyl 알코올glycosides다.17-19번 화합물은 새로운 화합물로 monniera-side I-III로 명명되었으며, 분광 분석에 의해 결정된 구조를 가지고 있다.Monniera-side I는 α 가 될-[2-0-(4-hydroxybenzoyl-β-D-pyranoglucosyl]-4-hydroxyphenethyl 알코올;Monniera-side II는 α 가 될-[2-0-(3-methoxy-4-hydroxy cinnamoyl)-β-D-pyranoglucoside] 3~, 4-dihydroxybenzyl 알코올;monniera-side III은 α 가 될-[2-0-(4-hydroxybenzoyl)-β-D-pyranoglucoside] 3~, 4-dihydroxybenzyl 알코올이다.phenethyl 알코올이다.화합물 20은 알려진 이성질체 플랜틴 글리코사이드 B이다.

호우 등이 [4] 새로 2 마리를 격리하여 확인했다phenethyl glycosides, named bacopa-side B and C (21, 22),      with structures corresponding to 3,4-dihydroxybenzyl alcohol (2-O- feruloyl)-β-D-glucopyranoside; and phenethyl alcohol [5-O-p-hydroxybenzoyl-β-D-furanocelulosyl-(1→2)]-β -D-pyranoglucoside.

1.3기타 화합물

의 n-butanol-soluble의 2대 1로 부분 부분 추출 Bm 메탄올 크로마토그래피 후, thin-layer 크로마토그래피에 의해 분석 되었20P MCI 젤 CHP (H ₂ O-MeOH, 1:0 0:1), dextran LH-20 열 (60% MeOH)과 Cosmosil C ₁ ₈-OPN (H ₂ O-MeOH,:10 1:1),도 양보 matsutake 알코올 (술 matsutaka) 파생, 구조 (3R)과-1-octan-3-yl-(6-O-sulfonyl)-β-D-glucopyranosyl, 이름bocapaside 한(23) [14]이다.

2 약리학적 효과

B. morio (Bm)는 저혈당, 항우울제, 항궤양, 항라멜라, 평활근 이완제, 및 등 다양한 약리 학적 활동을 보인다antioxidant effects. This review summarizes its pharmacological activities in seven aspects: hypoglycemic, central nervous system effects, antiulcer, and hepatoprotective activities.

2.1 Hypoglycemic

Bm에서 분리한 24가지 화합물을 대상으로에 대한 항 고혈당 활성을 검사하였다당뇨병에 걸린 쥐streptozotocin에 의해 유도되었다.그 결과 calcerorio-side B, marytynoside, luteolin-7-O-glucuronide 세 가지 화합물이 1 mmol/kg의 용량에서 중증의 저혈당 활성을 나타내었다 [4,12].

2.2 중심 효과

2.2.1 scopolamine의 길항

Scopolamine (3 mg/kg, i.p.) was used to induce passive avoidance in mice to test anti-dementia activity. the results showed that the Bm standard extract (containing 38% pseudoparkin saponin A) at 30 mg/kg could antagonize the dementia-inducing effects of scopolamine; in vitro, it exhibited significant anticholinesterase (AChE) activity, which was dose-dependent [13].

2.2.2 Antidepressant

Sairam¹4] conducted antidepressant activity tests using a methanol standard extract of Bacopa Monnieri and compared it with the standard antidepressant imipramine (15 mg/kg, ip). Rats were orally administered 20 and 40 mg/kg of the extract daily for 5 days, and significant antidepressant activity was observed in depression models such as forced swimming and acquired helplessness.

2.2.3 Prevention of NO-induced DNA damage

Activated astrocytes can produce high levels of NO, which may contribute to the onset of various neurodegenerative diseases. In rat astrocyte cultures, NO and S-nitroso-N-acetylpenicillanide induced the production of reactive species and DNA fragmentation in the genome. Treatment with Bacopa Monnieri methanol extract inhibited the formation of reactive products and DNA damage, with a dose-dependent effect. These biological activities suggest that Bm has therapeutic or preventive effects against various neurodegenerative diseases (such as dementia, epilepsy, and local ischemia) [15].

2.2.4 Reducing morphine withdrawal reactions

Sumathy [16] evaluated the effects of Bacopa Monnieri whole plant ethanol extracts on morphine withdrawal reactions in isolated guinea pig ileum. In vitro, guinea pig ileum exposed to morphine for 4 minutes was treated with naloxone to induce strong ileal contractions; 15 minutes before morphine exposure,   the addition of Bm ethanol extract at different concentrations (100–1000 μg/mL) significantly reduced naloxone-induced contractions in a dose-dependent manner. These results suggest that Bm may be effective against the syndrome induced by morphine withdrawal [16].

2.2.5 Protecting brain mitochondrial enzymes

Sumathy [17] investigated the protective effects of Bm ethanol extracts on changes in brain mitochondrial enzyme status induced by morphine in rats. Morphine-treated rats exhibited significantly lower levels of brain mitochondrial enzymes compared to control animals; however, when Bm extracts (40 mg/kg) were administered orally 2 hours prior to morphine administration, mitochondrial enzyme levels were maintained at normal levels.

2.2.6 Reducing the toxicity of antiepileptic drugs

Many epilepsy patients experience cognitive dysfunction due to the use of the antiepileptic drug phenytoin (PHT). Vohora[1$ investigated the protective effects of Bm against PHT-induced cognitive impairments in mice. The effects of Bm alone and in combination with PHT were evaluated using passive avoidance, maximum electric shock seizures, and motor coordination tests. The results showed that Bm reversed PHT-induced damage, improving both memory acquisition and retention, without affecting PHT's anticonvulsant activity.

2.2.7 Anti-stress

Anti-stress pharmacological studies showed that the saponins from Bm can regulate the expression of Hsp70 and the activity of SOD and P450 in the brains of SD male rats. Pseudo-pigweed saponins were administered orally at doses of 20 and 40 mg/kg for 7 days, with the control group receiving distilled water. Stress was induced 2 hours after the last dose. Stress did not cause any significant changes in Hsp70 expression in any brain region of the two dose groups, while Hsp70 expression was significantly enhanced in all brain regions of the control group. SOD activity in the hippocampus was significantly reduced in the low-dose group and the control group, while SOD activity increased in the high-dose group. P450 activity was enhanced in all brain regions of single-stressed animals and the two dose groups [19].

2.3 Anti-ulcer

Bm fresh juice exhibited significant anti-ulcer activity. Experimental animals were administered Bm standard methanol extract at doses of 10–50 mg/kg orally twice daily for 5 days, and the extract demonstrated dose-dependent anti-ulcer activity in models of gastric ulcers induced by ethanol, aspirin, 2-hour cold stress, and 4-hour pyloric ligation. Bm methanol extract at 20 mg/kg, administered orally to rats twice daily for 10 days, completely healed 50% of acetylsalicylic acid-induced gastric ulcers. Studies on the mechanism of action of the extract on various mucosal damages in rats indicated that Bm methanol extract at 20 mg/kg did not affect gastric acid and pepsin secretion, increased mucin secretion, reduce mucosal cell detachment without affecting cell proliferation. Due to its significant antioxidant effects, Bm methanol extract may primarily exert its preventive and therapeutic effects on gastric ulcers by acting on mucosal defense factors [24].

2.4 Hepatoprotective effects

Bm ethanol extract has a protective effect against morphine-induced liver toxicity in rats. In the morphine-treated group, significant increases in liver lipid peroxidation and a marked decrease in liver antioxidant enzyme levels were observed. When rats were administered morphine concurrently with oral Bm ethanol extract, these changes were prevented, suggesting that Bm exerts a hepatoprotective effect in morphine-induced liver toxicity [25].

2.5 Antilamebricidal Activity

The single compound bacopas-aponin C isolated from Bm was administered in various forms, including free, lipid-bound, microspheres, and nanoparticles, to evaluate its antilamebricidal activity. The results showed that all formulations exhibited high activity, with efficacy inversely proportional to vesicle size. Histological and hematological analyses revealed no adverse effects on the liver or kidneys, suggesting potential clinical application for leishmaniasis treatment [26].

2.6 Smooth muscle relaxation

Bm ethanol extract exhibited inhibitory activity against spontaneous contractions of guinea pig ileum and rabbit jejunum, with IC₅₀ values of 24 and 136 μg/mL, respectively. Administration of 260 μg/mL extract significantly reduced contractions induced by acetylcholine (ACh) and histamine (0.0001–10 μmol/L) in the ileum. The contraction of the ileum induced by 1 μmol/L ACh was also inhibited by 100–70 μg/mL of the extract, with a dose-dependent effect, and the IC₅₀ was 285 μg/mL. This indicates that the ethanol extract of Bm has a direct effect on smooth muscle. The responses of rabbit blood vessels and jejunum induced by CaCl₂ were attenuated by 10–700 μg/mL of Bm ethanol extract, suggesting that the extract directly interferes with the influx of calcium ions into cells. However, Bm extract had no effect on contractions induced by norepinephrine or caffeine, indicating that it does not affect intracellular calcium flow. The smooth muscle relaxant effect of Bm extract primarily acts through voltage-gated and receptor-mediated calcium channels, inhibiting calcium influx into the cell membrane [27].

The various solvent fractions and subfractions isolated from Bm significantly inhibited carbachol-induced bronchoconstriction, blood pressure reduction, and bradycardia in anesthetized rats. In vitro, crude extracts, petroleum ether, and methanol fractions inhibited KCl-induced tracheal constriction. The petroleum ether, dichloromethane, and methanol fractions exhibit 2–2.6 times the relaxing effect on pulmonary artery vessels compared to the crude extract. The CHCl₃-MeOH fraction significantly reduces ACh, BaCl₂, KCl, and CaCl₂-induced ileal contractions in guinea pigs, indicating that calcium ion flux is disrupted [28].

2.7 Antioxidant activity

The ethanol and hexane extracts of Bm have an inhibitory effect on lipid peroxidation induced by FeSO₄ and cumene hydroperoxide. The alcohol extracts exhibit strong protective effects. Compared with known antioxidants such as trimethylaminomethane, EDTA, and 비타민 E, Bm is a potent antioxidant with a dose-dependent effect. Bm ethanol extract at 100 μg is equivalent to 247 μg of EDTA and 58 μg of vitamin E²⁹.

Bm standard extracts at 5 and 10 mg/kg were administered orally to rats once daily for 7, 14, and 21 days, and the antioxidant enzyme activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the cerebral cortex, striatum, and hippocampus, with a dose-dependent effect. In contrast, the antioxidant agent silibinin [(1)-de-prenyl] (2 mg/kg, po) only increased the activity of SOD, CAT, and GPx in the cerebral cortex and striatum, but had no effect on these three enzymes in the hippocampus. Bm can increase the scavenging activity of oxidative free radicals, thereby benefiting cognitive function [30].

Analysis using nitroblue tetrazolium (NBT) showed that the ethanol extract of Bm whole plant inhibited the release of superoxide radicals from polymorphonuclear cells. This effect is attributed to the main saponins in the whole plant, including  pseudoparkin saponin A₃, at concentrations of 200, 100, 50, and 25 μg/mL, which exhibited inhibitory effects on NBT at 85%, 91.66%, 91. 66%, and 83%, respectively, with an IC₅₀ of 10.22 μg/mL. The positive controls, quercetin and vitamin C, had IC₅₀ values of 111 and 14.16 μg/mL, respectively. Another major component of Bm, bacopasaponin C, exhibited weak activity [31].

3 Clinical Improvement of Cognitive Function

Bm (300 mg) or placebo was administered to 건강 한 individuals in a double-blind study to assess cognitive function over a 12-week period. Neuropsychological tests included IT, learning rate, and memory consolidation. The results showed a significant improvement in visual information processing speed, indicating that Bm can significantly enhance cognitive processes, with the key factor being the continuous input of information from the environment for learning and memory [20].

Roodenrys et al. [21] reported the effects of Bm on human memory. A randomized, double-blind, placebo-controlled study was conducted on 76 adults aged 40–65 years, using various memory function tests as indicators, divided into three stages: before the trial, 3 months after the trial, and 6 weeks after the trial completion. The results showed that Bm had a significant effect on the retention of new information but no effect on learning rate, indicating that Bm can reduce the rate of forgetting newly acquired information.

A study investigated the effects of Bm combined with ginkgo on human cognitive function. The results demonstrated enhanced memory and attention, suggesting its potential for treating Alzheimer's disease. Another study reported that Bm had no immediate effects on cognitive function in healthy individuals [22,23].

4 결론

The incidence of Alzheimer's disease is increasing annually, becoming a social issue that concerns governments and health departments in both developed and developing countries. Through the relentless efforts of scientists worldwide, utilizing various experimental animal models of dementia, at least 50 plant extracts and chemical components with anti-dementia activity have been screened from traditional and folk medicines. Huperzia serrata, an early-developed plant extract from China, and the currently developed plant extract from India, both serve as excellent examples. Huperzia serrata is distributed in provinces such as Yunnan, Guangdong, Fujian, and Taiwan in China, with abundant resources and good development potential. It is believed that new nootropics will continue to be discovered in the future for the treatment of dementia.

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